Analyzing the tradeoff between electrical complexity and accuracy in patient-specific computational models of deep brain stimulation.

PubMed

Howell, Bryan; McIntyre, Cameron C

2016-06-01

Deep brain stimulation (DBS) is an adjunctive therapy that is effective in treating movement disorders and shows promise for treating psychiatric disorders. Computational models of DBS have begun to be utilized as tools to optimize the therapy. Despite advancements in the anatomical accuracy of these models, there is still uncertainty as to what level of electrical complexity is adequate for modeling the electric field in the brain and the subsequent neural response to the stimulation. We used magnetic resonance images to create an image-based computational model of subthalamic DBS. The complexity of the volume conductor model was increased by incrementally including heterogeneity, anisotropy, and dielectric dispersion in the electrical properties of the brain. We quantified changes in the load of the electrode, the electric potential distribution, and stimulation thresholds of descending corticofugal (DCF) axon models. Incorporation of heterogeneity altered the electric potentials and subsequent stimulation thresholds, but to a lesser degree than incorporation of anisotropy. Additionally, the results were sensitive to the choice of method for defining anisotropy, with stimulation thresholds of DCF axons changing by as much as 190%. Typical approaches for defining anisotropy underestimate the expected load of the stimulation electrode, which led to underestimation of the extent of stimulation. More accurate predictions of the electrode load were achieved with alternative approaches for defining anisotropy. The effects of dielectric dispersion were small compared to the effects of heterogeneity and anisotropy. The results of this study help delineate the level of detail that is required to accurately model electric fields generated by DBS electrodes.

Analyzing the tradeoff between electrical complexity and accuracy in patient-specific computational models of deep brain stimulation

NASA Astrophysics Data System (ADS)

Howell, Bryan; McIntyre, Cameron C.

2016-06-01

Objective. Deep brain stimulation (DBS) is an adjunctive therapy that is effective in treating movement disorders and shows promise for treating psychiatric disorders. Computational models of DBS have begun to be utilized as tools to optimize the therapy. Despite advancements in the anatomical accuracy of these models, there is still uncertainty as to what level of electrical complexity is adequate for modeling the electric field in the brain and the subsequent neural response to the stimulation. Approach. We used magnetic resonance images to create an image-based computational model of subthalamic DBS. The complexity of the volume conductor model was increased by incrementally including heterogeneity, anisotropy, and dielectric dispersion in the electrical properties of the brain. We quantified changes in the load of the electrode, the electric potential distribution, and stimulation thresholds of descending corticofugal (DCF) axon models. Main results. Incorporation of heterogeneity altered the electric potentials and subsequent stimulation thresholds, but to a lesser degree than incorporation of anisotropy. Additionally, the results were sensitive to the choice of method for defining anisotropy, with stimulation thresholds of DCF axons changing by as much as 190%. Typical approaches for defining anisotropy underestimate the expected load of the stimulation electrode, which led to underestimation of the extent of stimulation. More accurate predictions of the electrode load were achieved with alternative approaches for defining anisotropy. The effects of dielectric dispersion were small compared to the effects of heterogeneity and anisotropy. Significance. The results of this study help delineate the level of detail that is required to accurately model electric fields generated by DBS electrodes.

Bio-heat transfer model of deep brain stimulation-induced temperature changes

NASA Astrophysics Data System (ADS)

Elwassif, Maged M.; Kong, Qingjun; Vazquez, Maribel; Bikson, Marom

2006-12-01

There is a growing interest in the use of chronic deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. Fundamental questions remain about the physiologic effects of DBS. Previous basic research studies have focused on the direct polarization of neuronal membranes by electrical stimulation. The goal of this paper is to provide information on the thermal effects of DBS using finite element models to investigate the magnitude and spatial distribution of DBS-induced temperature changes. The parameters investigated include stimulation waveform, lead selection, brain tissue electrical and thermal conductivities, blood perfusion, metabolic heat generation during the stimulation and lead thermal conductivity/heat dissipation through the electrode. Our results show that clinical DBS protocols will increase the temperature of surrounding tissue by up to 0.8 °C depending on stimulation/tissue parameters.

Orientation selective deep brain stimulation

NASA Astrophysics Data System (ADS)

Lehto, Lauri J.; Slopsema, Julia P.; Johnson, Matthew D.; Shatillo, Artem; Teplitzky, Benjamin A.; Utecht, Lynn; Adriany, Gregor; Mangia, Silvia; Sierra, Alejandra; Low, Walter C.; Gröhn, Olli; Michaeli, Shalom

2017-02-01

Objective. Target selectivity of deep brain stimulation (DBS) therapy is critical, as the precise locus and pattern of the stimulation dictates the degree to which desired treatment responses are achieved and adverse side effects are avoided. There is a clear clinical need to improve DBS technology beyond currently available stimulation steering and shaping approaches. We introduce orientation selective neural stimulation as a concept to increase the specificity of target selection in DBS. Approach. This concept, which involves orienting the electric field along an axonal pathway, was tested in the corpus callosum of the rat brain by freely controlling the direction of the electric field on a plane using a three-electrode bundle, and monitoring the response of the neurons using functional magnetic resonance imaging (fMRI). Computational models were developed to further analyze axonal excitability for varied electric field orientation. Main results. Our results demonstrated that the strongest fMRI response was observed when the electric field was oriented parallel to the axons, while almost no response was detected with the perpendicular orientation of the electric field relative to the primary fiber tract. These results were confirmed by computational models of the experimental paradigm quantifying the activation of radially distributed axons while varying the primary direction of the electric field. Significance. The described strategies identify a new course for selective neuromodulation paradigms in DBS based on axonal fiber orientation.

A Programmable High-Voltage Compliance Neural Stimulator for Deep Brain Stimulation in Vivo

PubMed Central

Gong, Cihun-Siyong Alex; Lai, Hsin-Yi; Huang, Sy-Han; Lo, Yu-Chun; Lee, Nicole; Chen, Pin-Yuan; Tu, Po-Hsun; Yang, Chia-Yen; Lin, James Chang-Chieh; Chen, You-Yin

2015-01-01

Deep brain stimulation (DBS) is one of the most effective therapies for movement and other disorders. The DBS neurosurgical procedure involves the implantation of a DBS device and a battery-operated neurotransmitter, which delivers electrical impulses to treatment targets through implanted electrodes. The DBS modulates the neuronal activities in the brain nucleus for improving physiological responses as long as an electric discharge above the stimulation threshold can be achieved. In an effort to improve the performance of an implanted DBS device, the device size, implementation cost, and power efficiency are among the most important DBS device design aspects. This study aims to present preliminary research results of an efficient stimulator, with emphasis on conversion efficiency. The prototype stimulator features high-voltage compliance, implemented with only a standard semiconductor process, without the use of extra masks in the foundry through our proposed circuit structure. The results of animal experiments, including evaluation of evoked responses induced by thalamic electrical stimuli with our fabricated chip, were shown to demonstrate the proof of concept of our design. PMID:26029954

Detection of Alzheimer’s disease amyloid-beta plaque deposition by deep brain impedance profiling

NASA Astrophysics Data System (ADS)

Béduer, Amélie; Joris, Pierre; Mosser, Sébastien; Fraering, Patrick C.; Renaud, Philippe

2015-04-01

Objective. Alzheimer disease (AD) is the most common form of neurodegenerative disease in elderly people. Toxic brain amyloid-beta (Aß) aggregates and ensuing cell death are believed to play a central role in the pathogenesis of the disease. In this study, we investigated if we could monitor the presence of these aggregates by performing in situ electrical impedance spectroscopy measurements in AD model mice brains. Approach. In this study, electrical impedance spectroscopy measurements were performed post-mortem in APPPS1 transgenic mice brains. This transgenic model is commonly used to study amyloidogenesis, a pathological hallmark of AD. We used flexible probes with embedded micrometric electrodes array to demonstrate the feasibility of detecting senile plaques composed of Aß peptides by localized impedance measurements. Main results. We particularly focused on deep brain structures, such as the hippocampus. Ex vivo experiments using brains from young and old APPPS1 mice lead us to show that impedance measurements clearly correlate with the percentage of Aβ plaque load in the brain tissues. We could monitor the effects of aging in the AD APPPS1 mice model. Significance. We demonstrated that a localized electrical impedance measurement constitutes a valuable technique to monitor the presence of Aβ-plaques, which is complementary with existing imaging techniques. This method does not require prior Aβ staining, precluding the risk of variations in tissue uptake of dyes or tracers, and consequently ensuring reproducible data collection.

External trial deep brain stimulation device for the application of desynchronizing stimulation techniques.

PubMed

Hauptmann, C; Roulet, J-C; Niederhauser, J J; Döll, W; Kirlangic, M E; Lysyansky, B; Krachkovskyi, V; Bhatti, M A; Barnikol, U B; Sasse, L; Bührle, C P; Speckmann, E-J; Götz, M; Sturm, V; Freund, H-J; Schnell, U; Tass, P A

2009-12-01

In the past decade deep brain stimulation (DBS)-the application of electrical stimulation to specific target structures via implanted depth electrodes-has become the standard treatment for medically refractory Parkinson's disease and essential tremor. These diseases are characterized by pathological synchronized neuronal activity in particular brain areas. We present an external trial DBS device capable of administering effectively desynchronizing stimulation techniques developed with methods from nonlinear dynamics and statistical physics according to a model-based approach. These techniques exploit either stochastic phase resetting principles or complex delayed-feedback mechanisms. We explain how these methods are implemented into a safe and user-friendly device.

Magneto-electric nano-particles for non-invasive brain stimulation.

PubMed

Yue, Kun; Guduru, Rakesh; Hong, Jeongmin; Liang, Ping; Nair, Madhavan; Khizroev, Sakhrat

2012-01-01

This paper for the first time discusses a computational study of using magneto-electric (ME) nanoparticles to artificially stimulate the neural activity deep in the brain. The new technology provides a unique way to couple electric signals in the neural network to the magnetic dipoles in the nanoparticles with the purpose to enable a non-invasive approach. Simulations of the effect of ME nanoparticles for non-invasively stimulating the brain of a patient with Parkinson's Disease to bring the pulsed sequences of the electric field to the levels comparable to those of healthy people show that the optimized values for the concentration of the 20-nm nanoparticles (with the magneto-electric (ME) coefficient of 100 V cm(-1) Oe(-1) in the aqueous solution) is 3 × 10(6) particles/cc, and the frequency of the externally applied 300-Oe magnetic field is 80 Hz.

Experimental and theoretical characterization of the voltage distribution generated by deep brain stimulation.

PubMed

Miocinovic, Svjetlana; Lempka, Scott F; Russo, Gary S; Maks, Christopher B; Butson, Christopher R; Sakaie, Ken E; Vitek, Jerrold L; McIntyre, Cameron C

2009-03-01

Deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson's disease and shows great promise for numerous other disorders. While the fundamental purpose of DBS is to modulate neural activity with electric fields, little is known about the actual voltage distribution generated in the brain by DBS electrodes and as a result it is difficult to accurately predict which brain areas are directly affected by the stimulation. The goal of this study was to characterize the spatial and temporal characteristics of the voltage distribution generated by DBS electrodes. We experimentally recorded voltages around active DBS electrodes in either a saline bath or implanted in the brain of a non-human primate. Recordings were made during voltage-controlled and current-controlled stimulation. The experimental findings were compared to volume conductor electric field models of DBS parameterized to match the different experiments. Three factors directly affected the experimental and theoretical voltage measurements: 1) DBS electrode impedance, primarily dictated by a voltage drop at the electrode-electrolyte interface and the conductivity of the tissue medium, 2) capacitive modulation of the stimulus waveform, and 3) inhomogeneity and anisotropy of the tissue medium. While the voltage distribution does not directly predict the neural response to DBS, the results of this study do provide foundational building blocks for understanding the electrical parameters of DBS and characterizing its effects on the nervous system.

Neuromodulation, agency and autonomy.

PubMed

Glannon, Walter

2014-01-01

Neuromodulation consists in altering brain activity to restore mental and physical functions in individuals with neuropsychiatric disorders and brain and spinal cord injuries. This can be achieved by delivering electrical stimulation that excites or inhibits neural tissue, by using electrical signals in the brain to move computer cursors or robotic arms, or by displaying brain activity to subjects who regulate that activity by their own responses to it. As enabling prostheses, deep-brain stimulation and brain-computer interfaces (BCIs) are forms of extended embodiment that become integrated into the individual's conception of himself as an autonomous agent. In BCIs and neurofeedback, the success or failure of the techniques depends on the interaction between the learner and the trainer. The restoration of agency and autonomy through neuromodulation thus involves neurophysiological, psychological and social factors.

Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat.

PubMed

Wu, Hemmings; Ghekiere, Hartwin; Beeckmans, Dorien; Tambuyzer, Tim; van Kuyck, Kris; Aerts, Jean-Marie; Nuttin, Bart

2015-04-21

Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation.

Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat

PubMed Central

Wu, Hemmings; Ghekiere, Hartwin; Beeckmans, Dorien; Tambuyzer, Tim; van Kuyck, Kris; Aerts, Jean-Marie; Nuttin, Bart

2015-01-01

Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation. PMID:25897892

Neurosurgery of the future: Deep brain stimulations and manipulations.

PubMed

Nicolaidis, Stylianos

2017-04-01

Important advances are afoot in the field of neurosurgery-particularly in the realms of deep brain stimulation (DBS), deep brain manipulation (DBM), and the newly introduced refinement "closed-loop" deep brain stimulation (CLDBS). Use of closed-loop technology will make both DBS and DBM more precise as procedures and will broaden their indications. CLDBS utilizes as feedback a variety of sources of electrophysiological and neurochemical afferent information about the function of the brain structures to be treated or studied. The efferent actions will be either electric, i.e. the classic excitatory or inhibitory ones, or micro-injection of such things as neural proteins and transmitters, neural grafts, implants of pluripotent stem cells or mesenchymal stem cells, and some variants of gene therapy. The pathologies to be treated, beside Parkinson's disease and movement disorders, include repair of neural tissues, neurodegenerative pathologies, psychiatric and behavioral dysfunctions, i.e. schizophrenia in its various guises, bipolar disorders, obesity, anorexia, drug addiction, and alcoholism. The possibility of using these new modalities to treat a number of cognitive dysfunctions is also under consideration. Because the DBS-CLDBS technology brings about a cross-fertilization between scientific investigation and surgical practice, it will also contribute to an enhanced understanding of brain function. Copyright © 2017. Published by Elsevier Inc.

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

PubMed Central

Batra, Vinita; Guerin, Glenn F.; Goeders, Nicholas E.; Wilden, Jessica A.

2016-01-01

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug. PMID:26863392

Electro-Quasistatic Simulations in Bio-Systems Engineering and Medical Engineering

NASA Astrophysics Data System (ADS)

van Rienen, U.; Flehr, J.; Schreiber, U.; Schulze, S.; Gimsa, U.; Baumann, W.; Weiss, D. G.; Gimsa, J.; Benecke, R.; Pau, H.-W.

2005-05-01

Slowly varying electromagnetic fields play a key role in various applications in bio-systems and medical engineering. Examples are the electric activity of neurons on neurochips used as biosensors, the stimulating electric fields of implanted electrodes used for deep brain stimulation in patients with Morbus Parkinson and the stimulation of the auditory nerves in deaf patients, respectively. In order to simulate the neuronal activity on a chip it is necessary to couple Maxwell's and Hodgkin-Huxley's equations. First numerical results for a neuron coupling to a single electrode are presented. They show a promising qualitative agreement with the experimentally recorded signals. Further, simulations are presented on electrodes for deep brain stimulation in animal experiments where the question of electrode ageing and energy deposition in the surrounding tissue are of major interest. As a last example, electric simulations for a simple cochlea model are presented comparing the field in the skull bones for different electrode types and stimulations in different positions.

MRI-induced heating of deep brain stimulation leads

NASA Astrophysics Data System (ADS)

Mohsin, Syed A.; Sheikh, Noor M.; Saeed, Usman

2008-10-01

The radiofrequency (RF) field used in magnetic resonance imaging is scattered by medical implants. The scattered field of a deep brain stimulation lead can be very intense near the electrodes stimulating the brain. The effect is more pronounced if the lead behaves as a resonant antenna. In this paper, we examine the resonant length effect. We also use the finite element method to compute the near field for (i) the lead immersed in inhomogeneous tissue (fat, muscle, and brain tissues) and (ii) the lead connected to an implantable pulse generator. Electric field, specific absorption rate and induced temperature rise distributions have been obtained in the brain tissue surrounding the electrodes. The worst-case scenario has been evaluated by neglecting the effect of blood perfusion. The computed values are in good agreement with in vitro measurements made in the laboratory.

Violence, mental illness, and the brain – A brief history of psychosurgery: Part 2 – From the limbic system and cingulotomy to deep brain stimulation

PubMed Central

Faria, Miguel A.

2013-01-01

Knowledge of neuroscience flourished during and in the wake of the era of frontal lobotomy, as a byproduct of psychosurgery in the late 1930s and 1940s, revealing fascinating neural pathways and neurophysiologic mechanisms of the limbic system for the formulation of emotions, memory, and human behavior. The creation of the Klüver-Bucy syndrome in monkeys opened new horizons in the pursuit of knowledge in human behavior and neuropathology. In the 1950s specialized functional neurosurgery was developed in association with stereotactic neurosurgery; deep brain electrodes were implanted for more precise recording of brain electrical activity in the evaluation and treatment of intractable mental disorders, including schizophrenia, “pathologic aggression,” and psychomotor seizures in temporal lobe epilepsy. Psychosurgical procedures involved deep brain stimulation of the limbic system, as well as ablative procedures, such as cingulotomy and thalamotomy. The history of these developments up to the 21st century will continue in this three-part essay-editorial, exclusively researched and written for the readers of Surgical Neurology International. PMID:23776761

Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation

PubMed Central

Lysyansky, Borys; Rosenblum, Michael; Pikovsky, Arkady; Tass, Peter A.

2017-01-01

High-frequency (HF) deep brain stimulation (DBS) is the gold standard for the treatment of medically refractory movement disorders like Parkinson’s disease, essential tremor, and dystonia, with a significant potential for application to other neurological diseases. The standard setup of HF DBS utilizes an open-loop stimulation protocol, where a permanent HF electrical pulse train is administered to the brain target areas irrespectively of the ongoing neuronal dynamics. Recent experimental and clinical studies demonstrate that a closed-loop, adaptive DBS might be superior to the open-loop setup. We here combine the notion of the adaptive high-frequency stimulation approach, that aims at delivering stimulation adapted to the extent of appropriately detected biomarkers, with specifically desynchronizing stimulation protocols. To this end, we extend the delayed feedback stimulation methods, which are intrinsically closed-loop techniques and specifically designed to desynchronize abnormal neuronal synchronization, to pulsatile electrical brain stimulation. We show that permanent pulsatile high-frequency stimulation subjected to an amplitude modulation by linear or nonlinear delayed feedback methods can effectively and robustly desynchronize a STN-GPe network of model neurons and suggest this approach for desynchronizing closed-loop DBS. PMID:28273176

Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems—A Simulation Study

PubMed Central

Johansson, Johannes; Wårdell, Karin; Hemm, Simone

2018-01-01

The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome. PMID:29415442

Sing the mind electric - principles of deep brain stimulation.

PubMed

Kringelbach, Morten L; Green, Alexander L; Owen, Sarah L F; Schweder, Patrick M; Aziz, Tipu Z

2010-10-01

The remarkable efficacy of deep brain stimulation (DBS) for a range of treatment-resistant disorders is still not matched by a comparable understanding of the underlying neural mechanisms. Some progress has been made using translational research with a range of neuroscientific techniques, and here we review the most promising emerging principles. On balance, DBS appears to work by restoring normal oscillatory activity between a network of key brain regions. Further research using this causal neuromodulatory tool may provide vital insights into fundamental brain function, as well as guide targets for future treatments. In particular, DBS could have an important role in restoring the balance of the brain's default network and thus repairing the malignant brain states associated with affective disorders, which give rise to serious disabling problems such as anhedonia, the lack of pleasure. At the same time, it is important to proceed with caution and not repeat the errors from the era of psychosurgery. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

A foldable electrode array for 3D recording of deep-seated abnormal brain cavities

NASA Astrophysics Data System (ADS)

Kil, Dries; De Vloo, Philippe; Fierens, Guy; Ceyssens, Frederik; Hunyadi, Borbála; Bertrand, Alexander; Nuttin, Bart; Puers, Robert

2018-06-01

Objective. This study describes the design and microfabrication of a foldable thin-film neural implant and investigates its suitability for electrical recording of deep-lying brain cavity walls. Approach. A new type of foldable neural electrode array is presented, which can be inserted through a cannula. The microfabricated electrode is specifically designed for electrical recording of the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept is demonstrated by measurements in rat brain cavities. On implantation, the electrode array unfolds in the brain cavity, contacting the cavity walls and allowing recording at multiple anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching is described. Electrochemical characterization of the electrode is performed in addition to an in vivo experiment in which the implantation procedure and the unfolding of the electrode are tested and visualized. Main results. Electrochemical characterization validated the suitability of the electrode for in vivo use. CT imaging confirmed the unfolding of the electrode in the brain cavity and analysis of recorded local field potentials showed the ability to record neural signals of biological origin. Significance. The conducted research confirms that it is possible to record neural activity from the inside wall of brain cavities at various anatomical locations after a single implantation procedure. This opens up possibilities towards research of abnormal brain cavities and the clinical conditions associated with them, such as central post-stroke pain.

Mechanisms of deep brain stimulation

PubMed Central

Cheng, Jennifer J.; Eskandar, Emad N.

2015-01-01

Deep brain stimulation (DBS) is widely used for the treatment of movement disorders including Parkinson's disease, essential tremor, and dystonia and, to a lesser extent, certain treatment-resistant neuropsychiatric disorders including obsessive-compulsive disorder. Rather than a single unifying mechanism, DBS likely acts via several, nonexclusive mechanisms including local and network-wide electrical and neurochemical effects of stimulation, modulation of oscillatory activity, synaptic plasticity, and, potentially, neuroprotection and neurogenesis. These different mechanisms vary in importance depending on the condition being treated and the target being stimulated. Here we review each of these in turn and illustrate how an understanding of these mechanisms is inspiring next-generation approaches to DBS. PMID:26510756

Effect of deep brain stimulation on different speech subsystems in patients with multiple sclerosis.

PubMed

Pützer, Manfred; Barry, William John; Moringlane, Jean Richard

2007-11-01

The effect of deep brain stimulation on articulation and phonation subsystems in seven patients with multiple sclerosis (MS) was examined. Production parameters in fast syllable-repetitions were defined and measured, and the phonation quality during vowel productions was analyzed. Speech material was recorded for patients (with and without stimulation) and for a group of healthy control speakers. With stimulation, the precision of glottal and supraglottal articulatory gestures is reduced, whereas phonation has a greater tendency to be hyperfunctional in comparison with the healthy control data. Different effects on the two speech subsystems are induced by electrical stimulation of the thalamus in patients with MS.

Influence of the implanted pulse generator as reference electrode in finite element model of monopolar deep brain stimulation.

PubMed

Walckiers, Grégoire; Fuchs, Benjamin; Thiran, Jean-Philippe; Mosig, Juan R; Pollo, Claudio

2010-01-30

Electrical deep brain stimulation (DBS) is an efficient method to treat movement disorders. Many models of DBS, based mostly on finite elements, have recently been proposed to better understand the interaction between the electrical stimulation and the brain tissues. In monopolar DBS, clinically widely used, the implanted pulse generator (IPG) is used as reference electrode (RE). In this paper, the influence of the RE model of monopolar DBS is investigated. For that purpose, a finite element model of the full electric loop including the head, the neck and the superior chest is used. Head, neck and superior chest are made of simple structures such as parallelepipeds and cylinders. The tissues surrounding the electrode are accurately modelled from data provided by the diffusion tensor magnetic resonance imaging (DT-MRI). Three different configurations of RE are compared with a commonly used model of reduced size. The electrical impedance seen by the DBS system and the potential distribution are computed for each model. Moreover, axons are modelled to compute the area of tissue activated by stimulation. Results show that these indicators are influenced by the surface and position of the RE. The use of a RE model corresponding to the implanted device rather than the usually simplified model leads to an increase of the system impedance (+48%) and a reduction of the area of activated tissue (-15%). (c) 2009 Elsevier B.V. All rights reserved.

Parallel Radiofrequency Transmission for the Reduction of Heating in Deep Brain Stimulation Leads at 3T

NASA Astrophysics Data System (ADS)

McElcheran, Clare

Deep Brain Stimulation (DBS) is increasingly used to treat a variety of brain diseases by sending electrical impulses to deep brain nuclei through long, electrically conductive leads. Magnetic resonance imaging (MRI) of patients pre- and post-implantation is desirable to target and position the implant, to evaluate possible side-effects and to examine DBS patients who have other health conditions. Although MRI is the preferred modality for pre-operative planning, MRI post-implantation is limited due to the risk of high local power deposition, and therefore tissue heating, at the tip of the lead. The localized power deposition arises from currents induced in the leads caused by coupling with the radiofrequency (RF) transmission field during imaging. In this thesis, parallel RF transmission (pTx) is used to tailor the RF electric field to suppress coupling effects. Three pTx coil configurations with 2-elements, 4-elements, and 8-elements, respectively, were investigated. Optimal input voltages to minimize coupling, while maintaining RF magnetic field homogeneity, were determined using a Nelder-Mead optimization algorithm. Resulting electric and magnetic fields were compared to that of a 16-rung birdcage coil. Experimental validation was performed with a custom-built 4-element pTx coil. Three cases were investigated to develop and evaluate this technique. First, a Proof-of-Concept study was performed to investigate the case of a simple, uniform cylindrical phantom with a straight, perfectly conducting wire. Second, a heterogeneous subject with bilateral, curved implanted wires was investigated. Finally, the third case investigated realistic patient lead-trajectories obtained from intra-operative CT scans. In all three cases, specific absorption rate (SAR), a metric used to quantify power deposition which results in heating, was reduced by over 90%. Maximal reduction in SAR was obtained with the 8-element pTx coil. Magnetic field homogeneity was comparable to the birdcage coil for the 4- and 8-element pTx configurations. Although further research is required before clinical implementation, these initial results suggest that the concept of optimizing pTx to reduce DBS heating effects holds considerable promise.

Influence of serial electrical stimulations of perifornical and posterior hypothalamic orexin-containing neurons on regulation of sleep homeostasis and sleep-wakefulness cycle recovery from experimental comatose state and anesthesia-induced deep sleep.

PubMed

Chijavadze, E; Chkhartishvili, E; Babilodze, M; Maglakelidze, N; Nachkebia, N

2013-11-01

The work was aimed for the ascertainment of following question - whether Orexin-containing neurons of dorsal and lateral hypothalamic, and brain Orexinergic system in general, are those cellular targets which can speed up recovery of disturbed sleep homeostasis and accelerate restoration of sleep-wakefulness cycle phases during some pathological conditions - experimental comatose state and/or deep anesthesia-induced sleep. Study was carried out on white rats. Modeling of experimental comatose state was made by midbrain cytotoxic lesions at intra-collicular level.Animals were under artificial respiration and special care. Different doses of Sodium Ethaminal were used for deep anesthesia. 30 min after comatose state and/or deep anesthesia induced sleep serial electrical stimulations of posterior and/or perifornical hypothalamus were started. Stimulation period lasted for 1 hour with the 5 min intervals between subsequent stimulations applied by turn to the left and right side hypothalamic parts.EEG registration of cortical and hippocampal electrical activity was started immediately after experimental comatose state and deep anesthesia induced sleep and continued continuously during 72 hour. According to obtained new evidences, serial electrical stimulations of posterior and perifornical hypothalamic Orexin-containing neurons significantly accelerate recovery of sleep homeostasis, disturbed because of comatose state and/or deep anesthesia induced sleep. Speed up recovery of sleep homeostasis was manifested in acceleration of coming out from comatose state and deep anesthesia induced sleep and significant early restoration of sleep-wakefulness cycle behavioral states.

Improvement of two-photon microscopic imaging in deep regions of living mouse brains by utilizing a light source based on an electrically controllable gain-switched laser diode

NASA Astrophysics Data System (ADS)

Sawada, Kazuaki; Kawakami, Ryosuke; Fang, Yi-Cheng; Hung, Jui-Hung; Kozawa, Yuichi; Otomo, Kohei; Sato, Shunichi; Yokoyama, Hiroyuki; Nemoto, Tomomi

2018-02-01

In vivo two-photon microscopy is an advantageous technique for observing living mouse brains at high spatial resolutions. We previously used a 1064 nm high-power light source based on an electrically controllable gain-switched laser diode (maximum power: 4 W, repetition rate: 10 MHz, pulse width: 7.5 picoseconds) and successfully visualized EYFP expressing neurons at deeper regions in H-line mouse brains under living conditions. However, severe damages were frequently observed when the laser power after the objective lens was over 600 mW, suggesting that a higher average power might not be suitable for visualizing neural structures and functions at deep regions. To increase fluorescent signals as a strategy to avoid such invasions, here, we evaluated the effects of the excitation laser parameters such as the repetition rate (5 - 10 MHz), or the peak power, at the moderate average powers (10 - 500 mW), by taking the advantage that this electrically controllable light source could be used to change the repetition rate independently from the average power or the pulse width. The fluorescent signals of EYFP at layer V of the cerebral cortex were increased by approximately twofold when the repetition rate was decreased from 10 MHz to 5 MHz at the same average power. We also confirmed similar effects in the EYFP solution (335 μM) and fixed brain slices. These results suggest that in vivo two-photon microscopic imaging might be improved by increasing the peak power at the same average power while avoiding the severe damages in living brains.

Processes for design, construction and utilisation of arrays of light-emitting diodes and light-emitting diode-coupled optical fibres for multi-site brain light delivery

PubMed Central

Bernstein, Jacob G.; Allen, Brian D.; Guerra, Alexander A.; Boyden, Edward S.

2016-01-01

Optogenetics enables light to be used to control the activity of genetically targeted cells in the living brain. Optical fibers can be used to deliver light to deep targets, and LEDs can be spatially arranged to enable patterned light delivery. In combination, arrays of LED-coupled optical fibers can enable patterned light delivery to deep targets in the brain. Here we describe the process flow for making LED arrays and LED-coupled optical fiber arrays, explaining key optical, electrical, thermal, and mechanical design principles to enable the manufacturing, assembly, and testing of such multi-site targetable optical devices. We also explore accessory strategies such as surgical automation approaches as well as innovations to enable low-noise concurrent electrophysiology. PMID:26798482

Endovascular brain intervention and mapping in a dog experimental model using magnetically-guided micro-catheter technology.

PubMed

Kara, Tomas; Leinveber, Pavel; Vlasin, Michal; Jurak, Pavel; Novak, Miroslav; Novak, Zdenek; Chrastina, Jan; Czechowicz, Krzysztof; Belehrad, Milos; Asirvatham, Samuel J

2014-06-01

Despite the substantial progress that has been achieved in interventional cardiology and cardiac electrophysiology, endovascular intervention for the diagnosis and treatment of central nervous system (CNS) disorders such as stroke, epilepsy and CNS malignancy is still limited, particularly due to highly tortuous nature of the cerebral arterial and venous system. Existing interventional devices and techniques enable only limited and complicated access especially into intra-cerebral vessels. The aim of this study was to develop a micro-catheter magnetically-guided technology specifically designed for endovascular intervention and mapping in deep CNS vascular structures. Mapping of electrical brain activity was performed via the venous system on an animal dog model with the support of the NIOBE II system. A novel micro-catheter specially designed for endovascular interventions in the CNS, with the support of the NIOBE II technology, was able to reach safely deep intra-cerebral venous structures and map the electrical activity there. Such structures are not currently accessible using standard catheters. This is the first study demonstrating successful use of a new micro-catheter in combination with NIOBE II technology for endovascular intervention in the brain.

Conductive nanogel-interfaced neural microelectrode arrays with electrically controlled in-situ delivery of manganese ions enabling high-resolution MEMRI for synchronous neural tracing with deep brain stimulation.

PubMed

Huang, Wei-Chen; Lo, Yu-Chih; Chu, Chao-Yi; Lai, Hsin-Yi; Chen, You-Yin; Chen, San-Yuan

2017-04-01

Chronic brain stimulation has become a promising physical therapy with increased efficacy and efficiency in the treatment of neurodegenerative diseases. The application of deep brain electrical stimulation (DBS) combined with manganese-enhanced magnetic resonance imaging (MEMRI) provides an unbiased representation of the functional anatomy, which shows the communication between areas of the brain responding to the therapy. However, it is challenging for the current system to provide a real-time high-resolution image because the incorporated MnCl 2 solution through microinjection usually results in image blurring or toxicity due to the uncontrollable diffusion of Mn 2+ . In this study, we developed a new type of conductive nanogel-based neural interface composed of amphiphilic chitosan-modified poly(3,4 -ethylenedioxythiophene) (PMSDT) that can exhibit biomimic structural/mechanical properties and ionic/electrical conductivity comparable to that of Au. More importantly, the PMSDT enables metal-ligand bonding with Mn 2+ ions, so that the system can release Mn 2+ ions rather than MnCl 2 solution directly and precisely controlled by electrical stimulation (ES) to achieve real-time high-resolution MEMRI. With the integration of PMSDT nanogel-based coating in polyimide-based microelectrode arrays, the post-implantation DBS enables frequency-dependent MR imaging in vivo, as well as small focal imaging in response to channel site-specific stimulation on the implant. The MR imaging of the implanted brain treated with 5-min electrical stimulation showed a thalamocortical neuronal pathway after 36 h, confirming the effective activation of a downstream neuronal circuit following DBS. By eliminating the susceptibility to artifact and toxicity, this system, in combination with a MR-compatible implant and a bio-compliant neural interface, provides a harmless and synchronic functional anatomy for DBS. The study demonstrates a model of MEMRI-functionalized DBS based on functional neural interface engineering and controllable delivery technology, which can be utilized in more detailed exploration of the functional anatomy in the treatment of neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intra-operative recording of motor tract potentials at the cervico-medullary junction following scalp electrical and magnetic stimulation of the motor cortex.

PubMed Central

Thompson, P D; Day, B L; Crockard, H A; Calder, I; Murray, N M; Rothwell, J C; Marsden, C D

1991-01-01

Activity in descending motor pathways after scalp electrical and magnetic brain stimulation of the motor cortex was recorded from the exposed cervico-medullary junction in six patients having trans-oral surgery of the upper cervical spine. Recordings during deep anaesthesia without muscle paralysis revealed an initial negative potential (D wave) at about 2 ms with electrical stimulation in five of the six patients. This was followed by a muscle potential which obscured any later waveforms. Magnetic stimulation produced clear potentials in only one patient. The earliest wave to magnetic stimulation during deep anaesthesia was 1-2 ms later than the earliest potential to electrical stimulation. Following lightening of the anaesthetic and the administration of muscle relaxants a series of later negative potentials (I waves) were more clearly seen to both electrical and magnetic stimulation. More I waves were recorded to magnetic stimulation during light anaesthesia than during deep anaesthesia. Increasing the intensity of electrical stimulation also produced an extra late I wave. At the highest intensity of magnetic stimulation the latency of the earliest potential was comparable to the D wave to electrical stimulation. The intervals between these various D and I waves corresponded to those previously described for the timing of single motor unit discharge after cortical stimulation. PMID:1654395

From Nose to Brain: Un-Sensed Electrical Currents Applied in the Nose Alter Activity in Deep Brain Structures

PubMed Central

Weiss, Tali; Shushan, Sagit; Ravia, Aharon; Hahamy, Avital; Secundo, Lavi; Weissbrod, Aharon; Ben-Yakov, Aya; Holtzman, Yael; Cohen-Atsmoni, Smadar; Roth, Yehudah; Sobel, Noam

2016-01-01

Rules linking patterns of olfactory receptor neuron activation in the nose to activity patterns in the brain and ensuing odor perception remain poorly understood. Artificially stimulating olfactory neurons with electrical currents and measuring ensuing perception may uncover these rules. We therefore inserted an electrode into the nose of 50 human volunteers and applied various currents for about an hour in each case. This induced assorted non-olfactory sensations but never once the perception of odor. To validate contact with the olfactory path, we used functional magnetic resonance imaging to measure resting-state brain activity in 18 subjects before and after un-sensed stimulation. We observed stimulation-induced neural decorrelation specifically in primary olfactory cortex, implying contact with the olfactory path. These results suggest that indiscriminate olfactory activation does not equate with odor perception. Moreover, this effort serendipitously uncovered a novel path for minimally invasive brain stimulation through the nose. PMID:27591145

Neural hijacking: action of high-frequency electrical stimulation on cortical circuits.

PubMed

Cheney, P D; Griffin, D M; Van Acker, G M

2013-10-01

Electrical stimulation of the brain was one of the first experimental methods applied to understanding brain organization and function and it continues as a highly useful method both in research and clinical applications. Intracortical microstimulation (ICMS) involves applying electrical stimuli through a microelectrode suitable for recording the action potentials of single neurons. ICMS can be categorized into single-pulse stimulation; high-frequency, short-duration stimulation; and high-frequency, long-duration stimulation. For clinical and experimental reasons, considerable interest focuses on the mechanism of neural activation by electrical stimuli. In this article, we discuss recent results suggesting that action potentials evoked in cortical neurons by high-frequency electrical stimulation do not sum with the natural, behaviorally related background activity; rather, high-frequency stimulation eliminates and replaces natural activity. We refer to this as neural hijacking. We propose that a major component of the mechanism underlying neural hijacking is excitation of axons by ICMS and elimination of natural spikes by antidromic collision with stimulus-driven spikes evoked at high frequency. Evidence also supports neural hijacking as an important mechanism underlying the action of deep brain stimulation in the subthalamic nucleus and its therapeutic effect in treating Parkinson's disease.

Deep learning for hybrid EEG-fNIRS brain-computer interface: application to motor imagery classification.

PubMed

Chiarelli, Antonio Maria; Croce, Pierpaolo; Merla, Arcangelo; Zappasodi, Filippo

2018-06-01

Brain-computer interface (BCI) refers to procedures that link the central nervous system to a device. BCI was historically performed using electroencephalography (EEG). In the last years, encouraging results were obtained by combining EEG with other neuroimaging technologies, such as functional near infrared spectroscopy (fNIRS). A crucial step of BCI is brain state classification from recorded signal features. Deep artificial neural networks (DNNs) recently reached unprecedented complex classification outcomes. These performances were achieved through increased computational power, efficient learning algorithms, valuable activation functions, and restricted or back-fed neurons connections. By expecting significant overall BCI performances, we investigated the capabilities of combining EEG and fNIRS recordings with state-of-the-art deep learning procedures. We performed a guided left and right hand motor imagery task on 15 subjects with a fixed classification response time of 1 s and overall experiment length of 10 min. Left versus right classification accuracy of a DNN in the multi-modal recording modality was estimated and it was compared to standalone EEG and fNIRS and other classifiers. At a group level we obtained significant increase in performance when considering multi-modal recordings and DNN classifier with synergistic effect. BCI performances can be significantly improved by employing multi-modal recordings that provide electrical and hemodynamic brain activity information, in combination with advanced non-linear deep learning classification procedures.

Neuromodulation: Selected approaches and challenges

PubMed Central

Parpura, Vladimir; Silva, Gabriel A.; Tass, Peter A.; Bennet, Kevin E.; Meyyappan, Meyya; Koehne, Jessica; Lee, Kendall H.; Andrews, Russell J.

2012-01-01

The brain operates through complex interactions in the flow of information and signal processing within neural networks. The “wiring” of such networks, being neuronal or glial, can physically and/or functionally go rogue in various pathological states. Neuromodulation, as a multidisciplinary venture, attempts to correct such faulty nets. In this review, selected approaches and challenges in neuromoduation are discussed. The use of water-dispersible carbon nanotubes have proven effective in modulation of neurite outgrowth in culture as well as in aiding regeneration after spinal cord injury in vivo. Studying neural circuits using computational biology and analytical engineering approaches brings to light geometrical mapping of dynamics within neural networks, much needed information for stimulation interventions in medical practice. Indeed, sophisticated desynchronization approaches used for brain stimulation have been successful in coaxing “misfiring” neuronal circuits to resume productive firing patterns in various human disorders. Devices have been developed for the real time measurement of various neurotransmitters as well as electrical activity in the human brain during electrical deep brain stimulation. Such devices can establish the dynamics of electrochemical changes in the brain during stimulation. With increasing application of nanomaterials in devices for electrical and chemical recording and stimulating in the brain, the era of cellular, and even intracellular, precision neuromodulation will soon be upon us. PMID:23190025

[Deep brain stimulation in the treatment of movement disorders].

PubMed

Goto, Satoshi

2007-11-01

The introduction of deep brain stimulation (DBS) was a historical step forward for the treatment of advanced and medically intractable movement disorders that include Parkinson's disease, dystonias, essential tremor, and Holmes' tremor. DBS is able to modulate the target region electrically in a reversible and adjustable fashion in contrast to an irreversible and destructive lesioning procedure. In the treatment of movement disorders, the potential targets are the thalamic ventral intermediate nucleus (Vim), globus pallidus internus (GPi), subthalamic nucleus (STN), pedunculopontine nucleus (PPN), and thalamic Vo-complex nucleus. With the development of DBS technology and stereotactic neurosurgical techniques, its therapeutic efficacy has been increased while reducing surgical complications. DBS has become an established therapy for disabling movement disorders and is currently being used to treat neuropsychiatric disorders.

Long-term implantation of deep brain stimulation electrodes in the pontine micturition centre of the Göttingen minipig.

PubMed

Jensen, Kristian N; Deding, Dorthe; Sørensen, Jens Christian; Bjarkam, Carsten R

2009-07-01

To implant deep brain stimulation (DBS) electrodes in the porcine pontine micturition centre (PMC) in order to establish a large animal model of PMC-DBS. Brain stems from four Göttingen minipigs were sectioned coronally into 40-mum-thick histological sections and stained with Nissl, auto-metallographic myelin stain, tyrosine hydroxylase and corticotrophin-releasing factor immunohistochemistry in order to identify the porcine PMC. DBS electrodes were then stereotaxically implanted on the right side into the PMC in four Göttingen minipigs, and the bladder response to electrical stimulation was evaluated by subsequent cystometry performed immediately after the operation and several weeks later. A paired CRF-dense area homologous to the PMC in other species was encountered in the rostral pontine tegmentum medial to the locus coeruleus and ventral to the floor of the fourth ventricle. Electrical stimulation of the CRF-dense area resulted in an increased detrusor pressure followed by visible voiding in some instances. The pigs were allowed to survive between 14 and 55 days, and electrical stimulation resulting in an increased detrusor pressure was performed on more than one occasion without affecting consciousness or general thriving. None of the pigs developed postoperative infections or died prematurely. DBS electrodes can be implanted for several weeks in the identified CRF-dense area resulting in a useful large animal model for basic research on micturition and the future clinical use of this treatment modality in neurogenic supra-pontine voiding disorders.

Deep brain transcranial magnetic stimulation using variable "Halo coil" system

NASA Astrophysics Data System (ADS)

Meng, Y.; Hadimani, R. L.; Crowther, L. J.; Xu, Z.; Qu, J.; Jiles, D. C.

2015-05-01

Transcranial Magnetic Stimulation has the potential to treat various neurological disorders non-invasively and safely. The "Halo coil" configuration can stimulate deeper regions of the brain with lower surface to deep-brain field ratio compared to other coil configurations. The existing "Halo coil" configuration is fixed and is limited in varying the site of stimulation in the brain. We have developed a new system based on the current "Halo coil" design along with a graphical user interface system that enables the larger coil to rotate along the transverse plane. The new system can also enable vertical movement of larger coil. Thus, this adjustable "Halo coil" configuration can stimulate different regions of the brain by adjusting the position and orientation of the larger coil on the head. We have calculated magnetic and electric fields inside a MRI-derived heterogeneous head model for various positions and orientations of the coil. We have also investigated the mechanical and thermal stability of the adjustable "Halo coil" configuration for various positions and orientations of the coil to ensure safe operation of the system.

Developments in deep brain stimulation using time dependent magnetic fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crowther, L.J.; Nlebedim, I.C.; Jiles, D.C.

2012-03-07

The effect of head model complexity upon the strength of field in different brain regions for transcranial magnetic stimulation (TMS) has been investigated. Experimental measurements were used to verify the validity of magnetic field calculations and induced electric field calculations for three 3D human head models of varying complexity. Results show the inability for simplified head models to accurately determine the site of high fields that lead to neuronal stimulation and highlight the necessity for realistic head modeling for TMS applications.

Developments in deep brain stimulation using time dependent magnetic fields

NASA Astrophysics Data System (ADS)

Crowther, L. J.; Nlebedim, I. C.; Jiles, D. C.

2012-04-01

The effect of head model complexity upon the strength of field in different brain regions for transcranial magnetic stimulation (TMS) has been investigated. Experimental measurements were used to verify the validity of magnetic field calculations and induced electric field calculations for three 3D human head models of varying complexity. Results show the inability for simplified head models to accurately determine the site of high fields that lead to neuronal stimulation and highlight the necessity for realistic head modeling for TMS applications.

Recording and Modulation of Epileptiform Activity in Rodent Brain Slices Coupled to Microelectrode Arrays.

PubMed

Panuccio, Gabriella; Colombi, Ilaria; Chiappalone, Michela

2018-05-15

Temporal lobe epilepsy (TLE) is the most common partial complex epileptic syndrome and the least responsive to medications. Deep brain stimulation (DBS) is a promising approach when pharmacological treatment fails or neurosurgery is not recommended. Acute brain slices coupled to microelectrode arrays (MEAs) represent a valuable tool to study neuronal network interactions and their modulation by electrical stimulation. As compared to conventional extracellular recording techniques, they provide the added advantages of a greater number of observation points and a known inter-electrode distance, which allow studying the propagation path and speed of electrophysiological signals. However, tissue oxygenation may be greatly impaired during MEA recording, requiring a high perfusion rate, which comes at the cost of decreased signal-to-noise ratio and higher oscillations in the experimental temperature. Electrical stimulation further stresses the brain tissue, making it difficult to pursue prolonged recording/stimulation epochs. Moreover, electrical modulation of brain slice activity needs to target specific structures/pathways within the brain slice, requiring that electrode mapping be easily and quickly performed live during the experiment. Here, we illustrate how to perform the recording and electrical modulation of 4-aminopyridine (4AP)-induced epileptiform activity in rodent brain slices using planar MEAs. We show that the brain tissue obtained from mice outperforms rat brain tissue and is thus better suited for MEA experiments. This protocol guarantees the generation and maintenance of a stable epileptiform pattern that faithfully reproduces the electrophysiological features observed with conventional field potential recording, persists for several hours, and outlasts sustained electrical stimulation for prolonged epochs. Tissue viability throughout the experiment is achieved thanks to the use of a small-volume custom recording chamber allowing for laminar flow and quick solution exchange even at low (1 mL/min) perfusion rates. Quick MEA mapping for real-time monitoring and selection of stimulating electrodes is performed by a custom graphic user interface (GUI).

[An automatic system for anatomophysiological correlation in three planes simultaneously during functional neurosurgery].

PubMed

Teijeiro, E J; Macías, R J; Morales, J M; Guerra, E; López, G; Alvarez, L M; Fernández, F; Maragoto, C; Seijo, F; Alvarez, E

The Neurosurgical Deep Recording System (NDRS) using a personal computer takes the place of complex electronic equipment for recording and processing deep cerebral electrical activity, as a guide in stereotaxic functional neurosurgery. It also permits increased possibilities of presenting information in direct graphic form with automatic management and sufficient flexibility to implement different analyses. This paper describes the possibilities of automatic simultaneous graphic representation in three almost orthogonal planes, available with the new 5.1 version of NDRS so as to facilitate the analysis of anatomophysiological correlation in the localization of deep structures of the brain during minimal access surgery. This new version can automatically show the spatial behaviour of signals registered throughout the path of the electrode inside the brain, superimposed simultaneously on sagittal, coronal and axial sections of an anatomical atlas of the brain, after adjusting the scale automatically according to the dimensions of the brain of each individual patient. This may also be shown in a tridimensional representation of the different planes themselves intercepting. The NDRS system has been successfully used in Spain and Cuba in over 300 functional neurosurgery operations. The new version further facilitates analysis of spatial anatomophysiological correlation for the localization of brain structures. This system has contributed to increase the precision and safety in selecting surgical targets in the control of Parkinson s disease and other disorders of movement.

Desynchronizing electrical and sensory coordinated reset neuromodulation

PubMed Central

Popovych, Oleksandr V.; Tass, Peter A.

2012-01-01

Coordinated reset (CR) stimulation is a desynchronizing stimulation technique based on timely coordinated phase resets of sub-populations of a synchronized neuronal ensemble. It has initially been computationally developed for electrical deep brain stimulation (DBS), to enable an effective desynchronization and unlearning of pathological synchrony and connectivity (anti-kindling). Here we computationally show for ensembles of spiking and bursting model neurons interacting via excitatory and inhibitory adaptive synapses that a phase reset of neuronal populations as well as a desynchronization and an anti-kindling can robustly be achieved by direct electrical stimulation or indirect (synaptically-mediated) excitatory and inhibitory stimulation. Our findings are relevant for DBS as well as for sensory stimulation in neurological disorders characterized by pathological neuronal synchrony. Based on the obtained results, we may expect that the local effects in the vicinity of a depth electrode (realized by direct stimulation of the neurons' somata or stimulation of axon terminals) and the non-local CR effects (realized by stimulation of excitatory or inhibitory efferent fibers) of deep brain CR neuromodulation may be similar or even identical. Furthermore, our results indicate that an effective desynchronization and anti-kindling can even be achieved by non-invasive, sensory CR neuromodulation. We discuss the concept of sensory CR neuromodulation in the context of neurological disorders. PMID:22454622

Desynchronizing electrical and sensory coordinated reset neuromodulation.

PubMed

Popovych, Oleksandr V; Tass, Peter A

2012-01-01

Coordinated reset (CR) stimulation is a desynchronizing stimulation technique based on timely coordinated phase resets of sub-populations of a synchronized neuronal ensemble. It has initially been computationally developed for electrical deep brain stimulation (DBS), to enable an effective desynchronization and unlearning of pathological synchrony and connectivity (anti-kindling). Here we computationally show for ensembles of spiking and bursting model neurons interacting via excitatory and inhibitory adaptive synapses that a phase reset of neuronal populations as well as a desynchronization and an anti-kindling can robustly be achieved by direct electrical stimulation or indirect (synaptically-mediated) excitatory and inhibitory stimulation. Our findings are relevant for DBS as well as for sensory stimulation in neurological disorders characterized by pathological neuronal synchrony. Based on the obtained results, we may expect that the local effects in the vicinity of a depth electrode (realized by direct stimulation of the neurons' somata or stimulation of axon terminals) and the non-local CR effects (realized by stimulation of excitatory or inhibitory efferent fibers) of deep brain CR neuromodulation may be similar or even identical. Furthermore, our results indicate that an effective desynchronization and anti-kindling can even be achieved by non-invasive, sensory CR neuromodulation. We discuss the concept of sensory CR neuromodulation in the context of neurological disorders.

Evidence of transcranial direct current stimulation-generated electric fields at subthalamic level in human brain in vivo.

PubMed

Chhatbar, Pratik Y; Kautz, Steven A; Takacs, Istvan; Rowland, Nathan C; Revuelta, Gonzalo J; George, Mark S; Bikson, Marom; Feng, Wuwei

2018-03-13

Transcranial direct current stimulation (tDCS) is a promising brain modulation technique for several disease conditions. With this technique, some portion of the current penetrates through the scalp to the cortex and modulates cortical excitability, but a recent human cadaver study questions the amount. This insufficient intracerebral penetration of currents may partially explain the inconsistent and mixed results in tDCS studies to date. Experimental validation of a transcranial alternating current stimulation-generated electric field (EF) in vivo has been performed on the cortical (using electrocorticography, ECoG, electrodes), subcortical (using stereo electroencephalography, SEEG, electrodes) and deeper thalamic/subthalamic levels (using DBS electrodes). However, tDCS-generated EF measurements have never been attempted. We aimed to demonstrate that tDCS generates biologically relevant EF as deep as the subthalamic level in vivo. Patients with movement disorders who have implanted deep brain stimulation (DBS) electrodes serve as a natural experimental model for thalamic/subthalamic recordings of tDCS-generated EF. We measured voltage changes from DBS electrodes and body resistance from tDCS electrodes in three subjects while applying direct current to the scalp at 2 mA and 4 mA over two tDCS montages. Voltage changes at the level of deep nuclei changed proportionally with the level of applied current and varied with different tDCS montages. Our findings suggest that scalp-applied tDCS generates biologically relevant EF. Incorporation of these experimental results may improve finite element analysis (FEA)-based models. Copyright © 2018 Elsevier Inc. All rights reserved.

[EFFECTS OF ELECTRICAL STIMULATION OF NUCLEUS RETICULARIS PONTIS ORALIS ON THE SLEEP-WAKING STATES IN KRUSHINSKII-MOLODKINA STRAIN RATS].

PubMed

Vataev, S I; Malgina, N A; Oganesyan, G A

2015-07-01

The effects of electrical stimulation of nucleus reticularis pontis oralis on the behavior and brain electrical activity during all phases of the sleep-waking cycle was studied in Krushinskii-Molodkina strain rats, which have an inherited predisposition to audiogenic seizures. Electrical stimulation with 7 Hz frequency in the deep stage of slow-wave sleep cause appearance the fast-wave sleep. Similar stimulation during fast-wave sleep periods did not effects on the electrographic patterns and EEG spectral characteristics of hippocampus, visual, auditory and somatocnen nrnrenc nf the cnrtey ThPe sfimul1stinns did nnt break a fast-wave sleenhut increased almost twice due the duration of these sleep episodes. After electrical stimulation by same frequency during the wakeftlness and superficial slow-wave sleep states, the patterns and spectral characteristics of brain electrical activity in rats showed no significant changes as compared with controls. The results of this study indicate that the state of the animals sleep-waking cycle at the time of stimulation is a critical variable that influences the responses which are induced by electrical stimulation of the nucleus reticularis pontis oralis.

Central thalamic deep brain stimulation for support of forebrain arousal regulation in the minimally conscious state.

PubMed

Schiff, Nicholas D

2013-01-01

This chapter considers the use of central thalamic deep brain stimulation (CT/DBS) to support arousal regulation mechanisms in the minimally conscious state (MCS). CT/DBS for selected patients in a MCS is first placed in the historical context of prior efforts to use thalamic electrical brain stimulation to treat the unconscious clinical conditions of coma and vegetative state. These previous studies and a proof of concept result from a single-subject study of a patient in a MCS are reviewed against the background of new population data providing benchmarks of the natural history of vegetative and MCSs. The conceptual foundations for CT/DBS in selected patients in a MCS are then presented with consideration of both circuit and cellular mechanisms underlying recovery of consciousness identified from empirical studies. Directions for developing future generalizable criteria for CT/DBS that focus on the integrity of necessary brain systems and behavioral profiles in patients in a MCS that may optimally response to support of arousal regulation mechanisms are proposed. © 2013 Elsevier B.V. All rights reserved.

Language Mapping in Awake Surgery: Report of Two Cases with Review of Language Networks.

PubMed

Lim, Liang Hooi; Idris, Zamzuri; Reza, Faruque; Wan Hassan, Wan Mohd Nazaruddin; Mukmin, Laila Abd; Abdullah, Jafri Malin

2018-01-01

The role of language in communication plays a crucial role in human development and function. In patients who have a surgical lesion at the functional language areas, surgery should be intricately planned to avoid incurring further morbidity. This normally requires extensive functional and anatomical mappings of the brain to identify regions that are involved in language processing and production. In our case report, regions of the brain that are important for language functions were studied before surgery by employing (a) extraoperative methods such as functional magnetic resonance imaging, transmagnetic stimulation, and magnetoencephalography; (b) during the surgery by utilizing intraoperative awake surgical methods such as an intraoperative electrical stimulation; and (c) a two-stage surgery, in which electrical stimulation and first mapping are made thoroughly in the ward before second remapping during surgery. The extraoperative methods before surgery can guide the neurosurgeon to localize the functional language regions and tracts preoperatively. This will be confirmed using single-stage intraoperative electrical brain stimulation during surgery or a two-stage electrical brain stimulation before and during surgery. Here, we describe two cases in whom one has a superficial lesion and another a deep-seated lesion at language-related regions, in which language mapping was done to preserve its function. Additional review on the neuroanatomy of language regions, language network, and its impairment was also described.

Giovanni Aldini: from animal electricity to human brain stimulation.

PubMed

Parent, André

2004-11-01

Two hundred years ago, Giovanni Aldini published a highly influential book that reported experiments in which the principles of Luigi Galvani (animal electricity) and Alessandro Volta (bimetallic electricity) were used together for the first time. Aldini was born in Bologna in 1762 and graduated in physics at the University of his native town in 1782. As nephew and assistant of Galvani, he actively participated in a series of crucial experiments with frog's muscles that led to the idea that electricity was the long-sought vital force coursing from brain to muscles. Aldini became professor of experimental physics at the University of Bologna in 1798. He traveled extensively throughout Europe, spending much time defending the concept of his discreet uncle against the incessant attacks of Volta, who did not believe in animal electricity. Aldini used Volta's bimetallic pile to apply electric current to dismembered bodies of animals and humans; these spectacular galvanic reanimation experiments made a strong and enduring impression on his contemporaries. Aldini also treated patients with personality disorders and reported complete rehabilitation following transcranial administration of electric current. Aldini's work laid the ground for the development of various forms of electrotherapy that were heavily used later in the 19th century. Even today, deep brain stimulation, a procedure currently employed to relieve patients with motor or behavioral disorders, owes much to Aldini and galvanism. In recognition of his merits, Aldini was made a knight of the Iron Crown and a councillor of state at Milan, where he died in 1834.

Lightning may pose a danger to patients receiving deep brain stimulation: case report.

PubMed

Prezelj, Neža; Trošt, Maja; Georgiev, Dejan; Flisar, Dušan

2018-05-01

Deep brain stimulation (DBS) is an established treatment option for advanced stages of Parkinson's disease and other movement disorders. It is known that DBS is susceptible to strong electromagnetic fields (EMFs) that can be generated by various electrical devices at work, home, and in medical environments. EMFs can interfere with the proper functioning of implantable pulse generators (IPGs). Very strong EMFs can generate induction currents in implanted electrodes and even damage the brain. Manufacturers of DBS devices have issued a list of warnings on how to avoid this danger. Strong EMFs can result from natural forces as well. The authors present the case of a 66-year-old woman who was being treated with a rechargeable DBS system for neck dystonia when her apartment was struck by lightning. Domestic electronic devices that were operating during the event were burned and destroyed. The woman's IPG switched off but remained undamaged, and she suffered no neurological consequences.

Transcranial magnetic stimulation: Improved coil design for deep brain investigation

NASA Astrophysics Data System (ADS)

Crowther, L. J.; Marketos, P.; Williams, P. I.; Melikhov, Y.; Jiles, D. C.; Starzewski, J. H.

2011-04-01

This paper reports on a design for a coil for transcranial magnetic stimulation. The design shows potential for improving the penetration depth of the magnetic field, allowing stimulation of subcortical structures within the brain. The magnetic and induced electric fields in the human head have been calculated with finite element electromagnetic modeling software and compared with empirical measurements. Results show that the coil design used gives improved penetration depth, but also indicates the likelihood of stimulation of additional tissue resulting from the spatial distribution of the magnetic field.

Reconfigurable visible nanophotonic switch for optogenetic applications (Conference Presentation)

NASA Astrophysics Data System (ADS)

Mohanty, Aseema; Li, Qian; Tadayon, Mohammad Amin; Bhatt, Gaurang R.; Cardenas, Jaime; Miller, Steven A.; Kepecs, Adam; Lipson, Michal

2017-02-01

High spatiotemporal resolution deep-brain optical excitation for optogenetics would enable activation of specific neural populations and in-depth study of neural circuits. Conventionally, a single fiber is used to flood light into a large area of the brain with limited resolution. The scalability of silicon photonics could enable neural excitation over large areas with single-cell resolution similar to electrical probes. However, active control of these optical circuits has yet to be demonstrated for optogenetics. Here we demonstrate the first active integrated optical switch for neural excitation at 473 nm, enabling control of multiple beams for deep-brain neural stimulation. Using a silicon nitride waveguide platform, we develop a cascaded Mach-Zehnder interferometer (MZI) network located outside the brain to direct light to 8 different grating emitters located at the tip of the neural probe. We use integrated platinum microheaters to induce a local thermo-optic phase shift in the MZI to control the switch output. We measure an ON/OFF extinction ratio of >8dB for a single switch and a switching speed of 20 microseconds. We characterize the optical output of the switch by imaging its excitation of fluorescent dye. Finally, we demonstrate in vivo single-neuron optical activation from different grating emitters using a fully packaged device inserted into a mouse brain. Directly activated neurons showed robust spike firing activities with low first-spike latency and small jitter. Active switching on a nanophotonic platform is necessary for eventually controlling highly-multiplexed reconfigurable optical circuits, enabling high-resolution optical stimulation in deep-brain regions.

Carbon nanotube yarns for deep brain stimulation electrode.

PubMed

Jiang, Changqing; Li, Luming; Hao, Hongwei

2011-12-01

A new form of deep brain stimulation (DBS) electrode was proposed that was made of carbon nanotube yarns (CNTYs). Electrode interface properties were examined using cyclic voltammetry (CV) and electrochemical impedance spectrum (EIS). The CNTY electrode interface exhibited large charge storage capacity (CSC) of 12.3 mC/cm(2) which increased to 98.6 mC/cm(2) after acid treatment, compared with 5.0 mC/cm(2) of Pt-Ir. Impedance spectrum of both untreated and treated CNTY electrodes showed that finite diffusion process occurred at the interface due to their porous structure and charge was delivered through capacitive mechanism. To evaluate stability electrical stimulus was exerted for up to 72 h and CV and EIS results of CNTY electrodes revealed little alteration. Therefore CNTY could make a good electrode material for DBS.

Systems for deep brain stimulation: review of technical features.

PubMed

Amon, A; Alesch, F

2017-09-01

The use of deep brain stimulation (DBS) is an important treatment option for movement disorders and other medical conditions. Today, three major manufacturers provide implantable systems for DBS. Although the underlying principle is basically the same for all available systems, the differences in the technical features vary considerably. This article outlines aspects regarding the technical features of DBS systems. The differences between voltage and current sources are addressed and their effect on stimulation is shown. To maintain clinical benefit and minimize side effects the stimulation field has to be adapted to the requirements of the patient. Shaping of the stimulation field can be achieved by the electrode design and polarity configuration. Furthermore, the electric signal consisting of stimulation rate, stimulation amplitude and pulse width affect the stimulation field. Interleaving stimulation is an additional concept, which permits improved treatment outcomes. Therefore, the electrode design, the polarity, the electric signal, and the concept of interleaving stimulation are presented. The investigated systems can be also categorized as rechargeable and non-rechargeable, which is briefly discussed. Options for interconnecting different system components from various manufacturers are presented. The present paper summarizes the technical features and their combination possibilities, which can have a major impact on the therapeutic effect.

Comparison of Coil Designs for Transcranial Magnetic Stimulation on Mice

NASA Astrophysics Data System (ADS)

Rastogi, Priyam; Hadimani, Ravi; Jiles, David

2015-03-01

Transcranial magnetic stimulation (TMS) is a non-invasive treatment for neurological disorders using time varying magnetic field. The electric field generated by the time varying magnetic field is used to depolarize the brain neurons which can lead to measurable effects. TMS provides a surgical free method for the treatment of neurological brain disorders like depression, post-traumatic stress disorder, traumatic brain injury and Parkinson's disease. Before using TMS on human subjects, it is appropriate that its effects are verified on animals such as mice. The magnetic field intensity and stimulated region of the brain can be controlled by the shape, position and current in the coils. There are few reports on the designs of the coils for mice. In this paper, different types of coils are developed and compared using an anatomically realistic mouse model derived from MRI images. Parameters such as focality, depth of the stimulation, electric field strength on the scalp and in the deep brain regions, are taken into account. These parameters will help researchers to determine the most suitable coil design according to their need. This should result in improvements in treatment of specific disorders. Carver Charitable Trust.

Causal mapping of emotion networks in the human brain: Framework and initial findings.

PubMed

Dubois, Julien; Oya, Hiroyuki; Tyszka, J Michael; Howard, Matthew; Eberhardt, Frederick; Adolphs, Ralph

2017-11-13

Emotions involve many cortical and subcortical regions, prominently including the amygdala. It remains unknown how these multiple network components interact, and it remains unknown how they cause the behavioral, autonomic, and experiential effects of emotions. Here we describe a framework for combining a novel technique, concurrent electrical stimulation with fMRI (es-fMRI), together with a novel analysis, inferring causal structure from fMRI data (causal discovery). We outline a research program for investigating human emotion with these new tools, and provide initial findings from two large resting-state datasets as well as case studies in neurosurgical patients with electrical stimulation of the amygdala. The overarching goal is to use causal discovery methods on fMRI data to infer causal graphical models of how brain regions interact, and then to further constrain these models with direct stimulation of specific brain regions and concurrent fMRI. We conclude by discussing limitations and future extensions. The approach could yield anatomical hypotheses about brain connectivity, motivate rational strategies for treating mood disorders with deep brain stimulation, and could be extended to animal studies that use combined optogenetic fMRI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

PubMed Central

Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

2016-01-01

Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal modelling revealed a correlation between therapeutic effectiveness and attenuated within-region inhibitory connectivity in cerebellum. Finally, specific subregions of sensorimotor cortex were identified in which deep brain stimulation-evoked activation correlated with the presence of unwanted paraesthesias. These results suggest that thalamic deep brain stimulation in tremor likely exerts its effects through modulation of both olivocerebellar and thalamocortical circuits. In addition, our findings indicate that deep brain stimulation-evoked functional activation maps obtained intraoperatively may contain predictive information pertaining to the therapeutic and adverse effects induced by deep brain stimulation. PMID:27329768

Technical aspects of neurostimulation: Focus on equipment, electric field modeling, and stimulation protocols.

PubMed

Klooster, D C W; de Louw, A J A; Aldenkamp, A P; Besseling, R M H; Mestrom, R M C; Carrette, S; Zinger, S; Bergmans, J W M; Mess, W H; Vonck, K; Carrette, E; Breuer, L E M; Bernas, A; Tijhuis, A G; Boon, P

2016-06-01

Neuromodulation is a field of science, medicine, and bioengineering that encompasses implantable and non-implantable technologies for the purpose of improving quality of life and functioning of humans. Brain neuromodulation involves different neurostimulation techniques: transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS), which are being used both to study their effects on cognitive brain functions and to treat neuropsychiatric disorders. The mechanisms of action of neurostimulation remain incompletely understood. Insight into the technical basis of neurostimulation might be a first step towards a more profound understanding of these mechanisms, which might lead to improved clinical outcome and therapeutic potential. This review provides an overview of the technical basis of neurostimulation focusing on the equipment, the present understanding of induced electric fields, and the stimulation protocols. The review is written from a technical perspective aimed at supporting the use of neurostimulation in clinical practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Validation of a Portable Low-Power Deep Brain Stimulation Device Through Anxiolytic Effects in a Laboratory Rat Model.

PubMed

Kouzani, Abbas Z; Kale, Rajas P; Zarate-Garza, Pablo Patricio; Berk, Michael; Walder, Ken; Tye, Susannah J

2017-09-01

Deep brain stimulation (DBS) devices deliver electrical pulses to neural tissue through an electrode. To study the mechanisms and therapeutic benefits of deep brain stimulation, murine preclinical research is necessary. However, conducting naturalistic long-term, uninterrupted animal behavioral experiments can be difficult with bench-top systems. The reduction of size, weight, power consumption, and cost of DBS devices can assist the progress of this research in animal studies. A low power, low weight, miniature DBS device is presented in this paper. This device consists of electronic hardware and software components including a low-power microcontroller, an adjustable current source, an n-channel metal-oxide-semiconductor field-effect transistor, a coin-cell battery, electrode wires and a software program to operate the device. Evaluation of the performance of the device in terms of battery lifetime and device functionality through bench and in vivo tests was conducted. The bench test revealed that this device can deliver continuous stimulation current pulses of strength [Formula: see text], width [Formula: see text], and frequency 130 Hz for over 22 days. The in vivo tests demonstrated that chronic stimulation of the nucleus accumbens (NAc) with this device significantly increased psychomotor activity, together with a dramatic reduction in anxiety-like behavior in the elevated zero-maze test.

Direct Electrical Stimulation of the Human Entorhinal Region and Hippocampus Impairs Memory.

PubMed

Jacobs, Joshua; Miller, Jonathan; Lee, Sang Ah; Coffey, Tom; Watrous, Andrew J; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn; Gross, Robert E; Sheth, Sameer A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Kahana, Michael J; Rizzuto, Daniel S

2016-12-07

Deep brain stimulation (DBS) has shown promise for treating a range of brain disorders and neurological conditions. One recent study showed that DBS in the entorhinal region improved the accuracy of human spatial memory. Based on this line of work, we performed a series of experiments to more fully characterize the effects of DBS in the medial temporal lobe on human memory. Neurosurgical patients with implanted electrodes performed spatial and verbal-episodic memory tasks. During the encoding periods of both tasks, subjects received electrical stimulation at 50 Hz. In contrast to earlier work, electrical stimulation impaired memory performance significantly in both spatial and verbal tasks. Stimulation in both the entorhinal region and hippocampus caused decreased memory performance. These findings indicate that the entorhinal region and hippocampus are causally involved in human memory and suggest that refined methods are needed to use DBS in these regions to improve memory. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessing the direct effects of deep brain stimulation using embedded axon models

NASA Astrophysics Data System (ADS)

Sotiropoulos, Stamatios N.; Steinmetz, Peter N.

2007-06-01

To better understand the spatial extent of the direct effects of deep brain stimulation (DBS) on neurons, we implemented a geometrically realistic finite element electrical model incorporating anisotropic and inhomogenous conductivities. The model included the subthalamic nucleus (STN), substantia nigra (SN), zona incerta (ZI), fields of Forel H2 (FF), internal capsule (IC) and Medtronic 3387/3389 electrode. To quantify the effects of stimulation, we extended previous studies by using multi-compartment axon models with geometry and orientation consistent with anatomical features of the brain regions of interest. Simulation of axonal firing produced a map of relative changes in axonal activation. Voltage-controlled stimulation, with clinically typical parameters at the dorso-lateral STN, caused axon activation up to 4 mm from the target. This activation occurred within the FF, IC, SN and ZI with current intensities close to the average injected during DBS (3 mA). A sensitivity analysis of model parameters (fiber size, fiber orientation, degree of inhomogeneity, degree of anisotropy, electrode configuration) revealed that the FF and IC were consistently activated. Direct activation of axons outside the STN suggests that other brain regions may be involved in the beneficial effects of DBS when treating Parkinsonian symptoms.

Deep brain stimulation can regulate arterial blood pressure in awake humans.

PubMed

Green, Alexander L; Wang, Shouyan; Owen, Sarah L F; Xie, Kangning; Liu, Xuguang; Paterson, David J; Stein, John F; Bain, Peter G; Aziz, Tipu Z

2005-11-07

The periaqueductal grey matter is known to play a role in cardiovascular control in animals. Cardiovascular responses to electrical stimulation of the periventricular/periaqueductal grey matter were measured in 15 awake human study participants following implantation of deep brain stimulating electrodes for treatment of chronic pain. We found that stimulation of the ventral periventricular/periaqueductal grey matter caused a mean reduction in systolic blood pressure of 14.2+/-3.6 mmHg in seven patients and stimulation of the dorsal periventricular/periaqueductal grey matter caused a mean increase of 16.7+/-5.9 mmHg in six patients. A comparison between ventral and dorsal electrodes demonstrated significant differences (P<0.05). These changes were accompanied by analogous changes in diastolic blood pressure, pulse pressure, maximum dP/dt but not in the time interval between each R wave on the electrocardiogram.

Deep brain stimulation with a pre-existing cochlear implant: Surgical technique and outcome.

PubMed

Eddelman, Daniel; Wewel, Joshua; Wiet, R Mark; Metman, Leo V; Sani, Sepehr

2017-01-01

Patients with previously implanted cranial devices pose a special challenge in deep brain stimulation (DBS) surgery. We report the implantation of bilateral DBS leads in a patient with a cochlear implant. Technical nuances and long-term interdevice functionality are presented. A 70-year-old patient with advancing Parkinson's disease and a previously placed cochlear implant for sensorineural hearing loss was referred for placement of bilateral DBS in the subthalamic nucleus (STN). Prior to DBS, the patient underwent surgical removal of the subgaleal cochlear magnet, followed by stereotactic MRI, frame placement, stereotactic computed tomography (CT), and merging of imaging studies. This technique allowed for successful computational merging, MRI-guided targeting, and lead implantation with acceptable accuracy. Formal testing and programming of both the devices were successful without electrical interference. Successful DBS implantation with high resolution MRI-guided targeting is technically feasible in patients with previously implanted cochlear implants by following proper precautions.

Dr. Robert G. Heath: a controversial figure in the history of deep brain stimulation.

PubMed

O'Neal, Christen M; Baker, Cordell M; Glenn, Chad A; Conner, Andrew K; Sughrue, Michael E

2017-09-01

The history of psychosurgery is filled with tales of researchers pushing the boundaries of science and ethics. These stories often create a dark historical framework for some of the most important medical and surgical advancements. Dr. Robert G. Heath, a board-certified neurologist, psychiatrist, and psychoanalyst, holds a debated position within this framework and is most notably remembered for his research on schizophrenia. Dr. Heath was one of the first physicians to implant electrodes in deep cortical structures as a psychosurgical intervention. He used electrical stimulation in an attempt to cure patients with schizophrenia and as a method of conversion therapy in a homosexual man. This research was highly controversial, even prior to the implementation of current ethics standards for clinical research and often goes unmentioned within the historical narrative of deep brain stimulation (DBS). While distinction between the modern practice of DBS and its controversial origins is necessary, it is important to examine Dr. Heath's work as it allows for reflection on current neurosurgical practices and questioning the ethical implication of these advancements.

Investigation of Parallel Radiofrequency Transmission for the Reduction of Heating in Long Conductive Leads in 3 Tesla Magnetic Resonance Imaging

PubMed Central

McElcheran, Clare E.; Yang, Benson; Anderson, Kevan J. T.; Golenstani-Rad, Laleh; Graham, Simon J.

2015-01-01

Deep Brain Stimulation (DBS) is increasingly used to treat a variety of brain diseases by sending electrical impulses to deep brain nuclei through long, electrically conductive leads. Magnetic resonance imaging (MRI) of patients pre- and post-implantation is desirable to target and position the implant, to evaluate possible side-effects and to examine DBS patients who have other health conditions. Although MRI is the preferred modality for pre-operative planning, MRI post-implantation is limited due to the risk of high local power deposition, and therefore tissue heating, at the tip of the lead. The localized power deposition arises from currents induced in the leads caused by coupling with the radiofrequency (RF) transmission field during imaging. In the present work, parallel RF transmission (pTx) is used to tailor the RF electric field to suppress coupling effects. Electromagnetic simulations were performed for three pTx coil configurations with 2, 4, and 8-elements, respectively. Optimal input voltages to minimize coupling, while maintaining RF magnetic field homogeneity, were determined for all configurations using a Nelder-Mead optimization algorithm. Resulting electric and magnetic fields were compared to that of a 16-rung birdcage coil. Experimental validation was performed with a custom-built 4-element pTx coil. In simulation, 95-99% reduction of the electric field at the tip of the lead was observed between the various pTx coil configurations and the birdcage coil. Maximal reduction in E-field was obtained with the 8-element pTx coil. Magnetic field homogeneity was comparable to the birdcage coil for the 4- and 8-element pTx configurations. In experiment, a temperature increase of 2±0.15°C was observed at the tip of the wire using the birdcage coil, whereas negligible increase (0.2±0.15°C) was observed with the optimized pTx system. Although further research is required, these initial results suggest that the concept of optimizing pTx to reduce DBS heating effects holds considerable promise. PMID:26237218

Investigation of Parallel Radiofrequency Transmission for the Reduction of Heating in Long Conductive Leads in 3 Tesla Magnetic Resonance Imaging.

PubMed

McElcheran, Clare E; Yang, Benson; Anderson, Kevan J T; Golenstani-Rad, Laleh; Graham, Simon J

2015-01-01

Deep Brain Stimulation (DBS) is increasingly used to treat a variety of brain diseases by sending electrical impulses to deep brain nuclei through long, electrically conductive leads. Magnetic resonance imaging (MRI) of patients pre- and post-implantation is desirable to target and position the implant, to evaluate possible side-effects and to examine DBS patients who have other health conditions. Although MRI is the preferred modality for pre-operative planning, MRI post-implantation is limited due to the risk of high local power deposition, and therefore tissue heating, at the tip of the lead. The localized power deposition arises from currents induced in the leads caused by coupling with the radiofrequency (RF) transmission field during imaging. In the present work, parallel RF transmission (pTx) is used to tailor the RF electric field to suppress coupling effects. Electromagnetic simulations were performed for three pTx coil configurations with 2, 4, and 8-elements, respectively. Optimal input voltages to minimize coupling, while maintaining RF magnetic field homogeneity, were determined for all configurations using a Nelder-Mead optimization algorithm. Resulting electric and magnetic fields were compared to that of a 16-rung birdcage coil. Experimental validation was performed with a custom-built 4-element pTx coil. In simulation, 95-99% reduction of the electric field at the tip of the lead was observed between the various pTx coil configurations and the birdcage coil. Maximal reduction in E-field was obtained with the 8-element pTx coil. Magnetic field homogeneity was comparable to the birdcage coil for the 4- and 8-element pTx configurations. In experiment, a temperature increase of 2±0.15°C was observed at the tip of the wire using the birdcage coil, whereas negligible increase (0.2±0.15°C) was observed with the optimized pTx system. Although further research is required, these initial results suggest that the concept of optimizing pTx to reduce DBS heating effects holds considerable promise.

The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease.

PubMed

Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M; Tan, Huiling; Brown, Peter

2017-04-01

Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could be more efficacious than conventional continuous deep brain stimulation in the treatment of Parkinson's disease, and helps inform how adaptive deep brain stimulation might best be delivered. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

Centromedian-parafascicular deep brain stimulation induces differential functional inhibition of the motor, associative, and limbic circuits in large animals.

PubMed

Kim, Joo Pyung; Min, Hoon-Ki; Knight, Emily J; Duffy, Penelope S; Abulseoud, Osama A; Marsh, Michael P; Kelsey, Katherine; Blaha, Charles D; Bennet, Kevin E; Frye, Mark A; Lee, Kendall H

2013-12-15

Deep brain stimulation (DBS) of the centromedian-parafascicular (CM-Pf) thalamic nuclei has been considered an option for treating Tourette syndrome. Using a large animal DBS model, this study was designed to explore the network effects of CM-Pf DBS. The combination of DBS and functional magnetic resonance imaging is a powerful means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network in vivo. With a within-subjects design, we tested the proportional effects of CM and Pf DBS by manipulating current spread and varying stimulation contacts in healthy pigs (n = 5). Our results suggests that CM-Pf DBS has an inhibitory modulating effect in areas that have been suggested as contributing to impaired sensory-motor and emotional processing. The results also help to define the differential neural circuitry effects of the CM and Pf with evidence of prominent sensorimotor/associative effects for CM DBS and prominent limbic/associative effects for Pf DBS. Our results support the notion that stimulation of deep brain structures, such as the CM-Pf, modulates multiple networks with cortical effects. The networks affected by CM-Pf stimulation in this study reinforce the conceptualization of Tourette syndrome as a condition with psychiatric and motor symptoms and of CM-Pf DBS as a potentially effective tool for treating both types of symptoms. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Closed-Loop Neuromodulation Systems: Next-Generation Treatments for Psychiatric Illness

PubMed Central

Lo, Meng-Chen; Widge, Alik S.

2017-01-01

Despite deep brain stimulation’s positive early results in psychiatric disorders, well-designed clinical trials have yielded inconsistent clinical outcomes. One path to more reliable benefit is closed-loop therapy: stimulation that is automatically adjusted by a device or algorithm in response to changes in the patient’s electrical brain activity. These interventions may provide more precise and patient-specific treatments. In this article, we first introduce the available closed-loop neuromodulation platforms, which have shown clinical efficacy in epilepsy and strong early results in movement disorders. We discuss the strengths and limitations of these devices in the context of psychiatric illness. We then describe emerging technologies to address these limitations, including pre-clinical developments such as wireless deep neurostimulation and genetically targeted neuromodulation. Finally, we discuss ongoing challenges and limitations for closed-loop psychiatric brain stimulation development, most notably the difficulty of identifying meaningful biomarkers for titration. We consider this in the recently-released Research Domain Criteria (RDoC) framework and describe how neuromodulation and RDoC are jointly very well suited to address the problem of treatment-resistant illness. PMID:28523978

The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson’s disease

PubMed Central

Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M.; Tan, Huiling

2017-01-01

Abstract Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson’s disease, elevations in beta activity (13–35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson’s disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could be more efficacious than conventional continuous deep brain stimulation in the treatment of Parkinson’s disease, and helps inform how adaptive deep brain stimulation might best be delivered. PMID:28334851

Human Brain Activity Patterns beyond the Isoelectric Line of Extreme Deep Coma

PubMed Central

Kroeger, Daniel; Florea, Bogdan; Amzica, Florin

2013-01-01

The electroencephalogram (EEG) reflects brain electrical activity. A flat (isoelectric) EEG, which is usually recorded during very deep coma, is considered to be a turning point between a living brain and a deceased brain. Therefore the isoelectric EEG constitutes, together with evidence of irreversible structural brain damage, one of the criteria for the assessment of brain death. In this study we use EEG recordings for humans on the one hand, and on the other hand double simultaneous intracellular recordings in the cortex and hippocampus, combined with EEG, in cats. They serve to demonstrate that a novel brain phenomenon is observable in both humans and animals during coma that is deeper than the one reflected by the isoelectric EEG, and that this state is characterized by brain activity generated within the hippocampal formation. This new state was induced either by medication applied to postanoxic coma (in human) or by application of high doses of anesthesia (isoflurane in animals) leading to an EEG activity of quasi-rhythmic sharp waves which henceforth we propose to call ν-complexes (Nu-complexes). Using simultaneous intracellular recordings in vivo in the cortex and hippocampus (especially in the CA3 region) we demonstrate that ν-complexes arise in the hippocampus and are subsequently transmitted to the cortex. The genesis of a hippocampal ν-complex depends upon another hippocampal activity, known as ripple activity, which is not overtly detectable at the cortical level. Based on our observations, we propose a scenario of how self-oscillations in hippocampal neurons can lead to a whole brain phenomenon during coma. PMID:24058669

The functional neuroanatomy of pleasure and happiness.

PubMed

Kringelbach, Morten L; Berridge, Kent C

2010-06-01

Over fifty years ago the discovery that rats would work to electrically stimulate their brains suggested the intriguing possibility that bliss could be achieved through the use of 'pleasure electrodes' implanted deep within the brain. Subsequent research has failed to bring about this brave new world of boundless pleasure, but more recent findings have started to throw new light on the intriguing links between brain mechanisms of pleasure and happiness. We discuss these findings of the underlying neural mechanisms and functional neuroanatomy of pleasure in the brain. In particular we address how they may come to shed light on our understanding of the brain basis of happiness. Beyond sensory pleasures, we examine how higher pleasures may be related to the brain's default networks, especially in orchestrating cognitive aspects of the meaningfulness important to happiness. We also address how understanding of the hedonic brain might help alleviate the suffering caused by the lack of pleasure, anhedonia, which is a central feature of affective disorders such as depression and chronic pain.

Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation.

PubMed

Grill, Warren M; Cantrell, Meredith B; Robertson, Matthew S

2008-02-01

Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.

Chasing Tics in the Human Brain: Development of Open, Scheduled and Closed Loop Responsive Approaches to Deep Brain Stimulation for Tourette Syndrome

PubMed Central

Martinez-Ramirez, Daniel; Rossi, Peter J.; Peng, Zhongxing; Gunduz, Aysegul; Okun, Michael S.

2015-01-01

Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome. PMID:25851890

MR Anatomy of Deep Brain Nuclei with Special Reference to Specific Diseases and Deep Brain Stimulation Localization

PubMed Central

Telford, Ryan; Vattoth, Surjith

2014-01-01

Summary Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures. PMID:24571832

Differential impact of thalamic versus subthalamic deep brain stimulation on lexical processing.

PubMed

Krugel, Lea K; Ehlen, Felicitas; Tiedt, Hannes O; Kühn, Andrea A; Klostermann, Fabian

2014-10-01

Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation. Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects. Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON-OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson' disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation. In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way. Copyright © 2014 Elsevier Ltd. All rights reserved.

High permeability cores to optimize the stimulation of deeply located brain regions using transcranial magnetic stimulation

NASA Astrophysics Data System (ADS)

Salvador, R.; Miranda, P. C.; Roth, Y.; Zangen, A.

2009-05-01

Efficient stimulation of deeply located brain regions with transcranial magnetic stimulation (TMS) poses many challenges, arising from the fact that the induced field decays rapidly and becomes less focal with depth. We propose a new method to improve the efficiency of TMS of deep brain regions that combines high permeability cores, to increase focality and field intensity, with a coil specifically designed to induce a field that decays slowly with increasing depth. The performance of the proposed design was investigated using the finite element method to determine the total electric field induced by this coil/core arrangement on a realistically shaped homogeneous head model. The calculations show that the inclusion of the cores increases the field's magnitude by as much as 25% while also decreasing the field's decay with depth along specific directions. The focality, as measured by the area where the field's norm is greater than 1/\\sqrt 2 of its maximum value, is also improved by as much as 15% with some core arrangements. The coil's inductance is not significantly increased by the cores. These results show that the presence of the cores might make this specially designed coil even more suited for the effective stimulation of deep brain regions.

The Functional Neuroanatomy of Pleasure and Happiness

PubMed Central

Kringelbach, Morten L.; Berridge, Kent C.

2010-01-01

Over fifty years ago the discovery that rats would work to electrically stimulate their brains suggested the intriguing possibility that bliss could be achieved through the use of ‘pleasure electrodes’ implanted deep within the brain. Subsequent research has failed to bring about this brave new world of boundless pleasure, but more recent findings have started to throw new light on the intriguing links between brain mechanisms of pleasure and happiness. We discuss these findings of the underlying neural mechanisms and functional neuroanatomy of pleasure in the brain. In particular we address how they may come to shed light on our understanding of the brain basis of happiness. Beyond sensory pleasures, we examine how higher pleasures may be related to the brain’s default networks, especially in orchestrating cognitive aspects of the meaningfulness important to happiness. We also address how understanding of the hedonic brain might help alleviate the suffering caused by the lack of pleasure, anhedonia, which is a central feature of affective disorders such as depression and chronic pain. PMID:20587348

Deep-brain-stimulation does not impair deglutition in Parkinson's disease.

PubMed

Lengerer, Sabrina; Kipping, Judy; Rommel, Natalie; Weiss, Daniel; Breit, Sorin; Gasser, Thomas; Plewnia, Christian; Krüger, Rejko; Wächter, Tobias

2012-08-01

A large proportion of patients with Parkinson's disease develop dysphagia during the course of the disease. Dysphagia in Parkinson's disease affects different phases of deglutition, has a strong impact on quality of life and may cause severe complications, i.e., aspirational pneumonia. So far, little is known on how deep-brain-stimulation of the subthalamic nucleus influences deglutition in PD. Videofluoroscopic swallowing studies on 18 patients with Parkinson's disease, which had been performed preoperatively, and postoperatively with deep-brain-stimulation-on and deep-brain-stimulation-off, were analyzed retrospectively. The patients were examined in each condition with three consistencies (viscous, fluid and solid). The 'New Zealand index for multidisciplinary evaluation of swallowing (NZIMES) Subscale One' for qualitative and 'Logemann-MBS-Parameters' for quantitative evaluation were assessed. Preoperatively, none of the patients presented with clinically relevant signs of dysphagia. While postoperatively, the mean daily levodopa equivalent dosage was reduced by 50% and deep-brain-stimulation led to a 50% improvement in motor symptoms measured by the UPDRS III, no clinically relevant influence of deep-brain-stimulation-on swallowing was observed using qualitative parameters (NZIMES). However quantitative parameters (Logemann scale) found significant changes of pharyngeal parameters with deep-brain-stimulation-on as compared to preoperative condition and deep-brain-stimulation-off mostly with fluid consistency. In Parkinson patients without dysphagia deep-brain-stimulation of the subthalamic nucleus modulates the pharyngeal deglutition phase but has no clinically relevant influence on deglutition. Further studies are needed to test if deep-brain-stimulation is a therapeutic option for patients with swallowing disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain.

PubMed

Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

2015-01-01

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS.

Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain

PubMed Central

Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

2015-01-01

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS. PMID:26193653

An in depth view of avian sleep.

PubMed

Beckers, Gabriël J L; Rattenborg, Niels C

2015-03-01

Brain rhythms occurring during sleep are implicated in processing information acquired during wakefulness, but this phenomenon has almost exclusively been studied in mammals. In this review we discuss the potential value of utilizing birds to elucidate the functions and underlying mechanisms of such brain rhythms. Birds are of particular interest from a comparative perspective because even though neurons in the avian brain homologous to mammalian neocortical neurons are arranged in a nuclear, rather than a laminar manner, the avian brain generates mammalian-like sleep-states and associated brain rhythms. Nonetheless, until recently, this nuclear organization also posed technical challenges, as the standard surface EEG recording methods used to study the neocortex provide only a superficial view of the sleeping avian brain. The recent development of high-density multielectrode recording methods now provides access to sleep-related brain activity occurring deep in the avian brain. Finally, we discuss how intracerebral electrical imaging based on this technique can be used to elucidate the systems-level processing of hippocampal-dependent and imprinting memories in birds. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Twiddler's syndrome in a patient with obsessive-compulsive disorder treated with deep brain stimulation].

PubMed

Moliz, Nicolás; Katati, Majed J; Iañez, Benjamín; García, Asunción; Yagui, Eskandar; Horcajadas, Ángel

2015-01-01

Twiddler's syndrome is a rare complication associated with implantable electrical stimulation devices. First described in a patient with a pacemaker, it is a known complication in the field of cardiology. However, it is not so recognised in the world of neurosurgery, in which it has been described in relation to deep brain stimulation (DBS) devices. Characterised by manipulating either consciously or unconsciously the generator of such devices, which causes it to rotate on itself, the syndrome causes the coiling of the wiring of these systems and can lead to their rupture or the displacement of intracranial electrodes. We describe a case of twiddler's syndrome in a patient treated with DBS for obsessive-compulsive disorder, in which clinical deterioration presented after a good initial response. Control radiographs revealed rotation of the wiring system and displacement of the intracranial electrodes. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Spinal cord stimulation alleviates motor deficits in a primate model of Parkinson disease.

PubMed

Santana, Maxwell B; Halje, Pär; Simplício, Hougelle; Richter, Ulrike; Freire, Marco Aurelio M; Petersson, Per; Fuentes, Romulo; Nicolelis, Miguel A L

2014-11-19

Although deep brain electrical stimulation can alleviate the motor symptoms of Parkinson disease (PD), just a small fraction of patients with PD can take advantage of this procedure due to its invasive nature. A significantly less invasive method--epidural spinal cord stimulation (SCS)--has been suggested as an alternative approach for symptomatic treatment of PD. However, the mechanisms underlying motor improvements through SCS are unknown. Here, we show that SCS reproducibly alleviates motor deficits in a primate model of PD. Simultaneous neuronal recordings from multiple structures of the cortico-basal ganglia-thalamic loop in parkinsonian monkeys revealed abnormal highly synchronized neuronal activity within each of these structures and excessive functional coupling among them. SCS disrupted this pathological circuit behavior in a manner that mimics the effects caused by pharmacological dopamine replacement therapy or deep brain stimulation. These results suggest that SCS should be considered as an additional treatment option for patients with PD. Copyright © 2014 Elsevier Inc. All rights reserved.

Fully Implantable Deep Brain Stimulation System with Wireless Power Transmission for Long-term Use in Rodent Models of Parkinson's Disease.

PubMed

Heo, Man Seung; Moon, Hyun Seok; Kim, Hee Chan; Park, Hyung Woo; Lim, Young Hoon; Paek, Sun Ha

2015-03-01

The purpose of this study to develop new deep-brain stimulation system for long-term use in animals, in order to develop a variety of neural prostheses. Our system has two distinguished features, which are the fully implanted system having wearable wireless power transfer and ability to change the parameter of stimulus parameter. It is useful for obtaining a variety of data from a long-term experiment. To validate our system, we performed pre-clinical test in Parkinson's disease-rat models for 4 weeks. Through the in vivo test, we observed the possibility of not only long-term implantation and stability, but also free movement of animals. We confirmed that the electrical stimulation neither caused any side effect nor damaged the electrodes. We proved possibility of our system to conduct the long-term pre-clinical test in variety of parameter, which is available for development of neural prostheses.

Sleep, consciousness and the spontaneous and evoked electrical activity of the brain. Is there a cortical integrating mechanism?

PubMed

Evans, B M

2003-02-01

The physiological mechanisms that underlie consciousness and unconsciousness are the sleep/wake mechanisms. Deep sleep is a state of physiological reversible unconsciousness. The change from that state to wakefulness is mediated by the reticular activating mechanism. The reverse change from wakefulness to sleep is also an active process effected by an arousal inhibitory mechanism based on a partial blockade of the thalamus and upper brain stem, associated with thalamic sleep spindles and also with cortical sub-delta activity (<1 Hz). The deactivation of the thalamus has been demonstrated both electrically and by positron emission tomography during deep sleep. Normally, wakefulness is associated with instant awareness (defined as the ability to integrate all sensory information from the external environment and the internal environment of the body). Awareness may be a function of the thalamo-cortical network in the cerebral hemispheres, which forms the final path of the sleep/wake mechanism. Anatomical and physiological studies suggest that there may be a double thalamo-cortical network; one relating to cortical and thalamic areas with specific functions and the other global, involving all cortical areas and so-called 'non-specific' thalamic nuclei. The global system might function as a cortical integrating mechanism permitting the spread of information between the specific cortical areas and thus underlying awareness. The global system may also be responsible for much of the spontaneous and evoked electrical activity of the brain. The cognitive change between sleep and wakefulness is accompanied by changes in the autonomic system, the cerebral blood flow and cerebral metabolism. Awareness is an essential component of total consciousness (defined as continuous awareness of the external and internal environment, both past and present, together with the emotions arising from it). In addition to awareness, full consciousness requires short-term and explicit memory and intact emotional responses.

Computational Modeling and Neuroimaging Techniques for Targeting during Deep Brain Stimulation

PubMed Central

Sweet, Jennifer A.; Pace, Jonathan; Girgis, Fady; Miller, Jonathan P.

2016-01-01

Accurate surgical localization of the varied targets for deep brain stimulation (DBS) is a process undergoing constant evolution, with increasingly sophisticated techniques to allow for highly precise targeting. However, despite the fastidious placement of electrodes into specific structures within the brain, there is increasing evidence to suggest that the clinical effects of DBS are likely due to the activation of widespread neuronal networks directly and indirectly influenced by the stimulation of a given target. Selective activation of these complex and inter-connected pathways may further improve the outcomes of currently treated diseases by targeting specific fiber tracts responsible for a particular symptom in a patient-specific manner. Moreover, the delivery of such focused stimulation may aid in the discovery of new targets for electrical stimulation to treat additional neurological, psychiatric, and even cognitive disorders. As such, advancements in surgical targeting, computational modeling, engineering designs, and neuroimaging techniques play a critical role in this process. This article reviews the progress of these applications, discussing the importance of target localization for DBS, and the role of computational modeling and novel neuroimaging in improving our understanding of the pathophysiology of diseases, and thus paving the way for improved selective target localization using DBS. PMID:27445709

Tractography patterns of subthalamic nucleus deep brain stimulation.

PubMed

Vanegas-Arroyave, Nora; Lauro, Peter M; Huang, Ling; Hallett, Mark; Horovitz, Silvina G; Zaghloul, Kareem A; Lungu, Codrin

2016-04-01

Deep brain stimulation therapy is an effective symptomatic treatment for Parkinson's disease, yet the precise mechanisms responsible for its therapeutic effects remain unclear. Although the targets of deep brain stimulation are grey matter structures, axonal modulation is known to play an important role in deep brain stimulation's therapeutic mechanism. Several white matter structures in proximity to the subthalamic nucleus have been implicated in the clinical benefits of deep brain stimulation for Parkinson's disease. We assessed the connectivity patterns that characterize clinically beneficial electrodes in Parkinson's disease patients, after deep brain stimulation of the subthalamic nucleus. We evaluated 22 patients with Parkinson's disease (11 females, age 57 ± 9.1 years, disease duration 13.3 ± 6.3 years) who received bilateral deep brain stimulation of the subthalamic nucleus at the National Institutes of Health. During an initial electrode screening session, one month after deep brain stimulation implantation, the clinical benefits of each contact were determined. The electrode was localized by coregistering preoperative magnetic resonance imaging and postoperative computer tomography images and the volume of tissue activated was estimated from stimulation voltage and impedance. Brain connectivity for the volume of tissue activated of deep brain stimulation contacts was assessed using probabilistic tractography with diffusion-tensor data. Areas most frequently connected to clinically effective contacts included the thalamus, substantia nigra, brainstem and superior frontal gyrus. A series of discriminant analyses demonstrated that the strength of connectivity to the superior frontal gyrus and the thalamus were positively associated with clinical effectiveness. The connectivity patterns observed in our study suggest that the modulation of white matter tracts directed to the superior frontal gyrus and the thalamus is associated with favourable clinical outcomes and may contribute to the therapeutic effects of deep brain stimulation. Our method can be further developed to reliably identify effective deep brain stimulation contacts and aid in the programming process. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Deep Learning for Brain MRI Segmentation: State of the Art and Future Directions.

PubMed

Akkus, Zeynettin; Galimzianova, Alfiia; Hoogi, Assaf; Rubin, Daniel L; Erickson, Bradley J

2017-08-01

Quantitative analysis of brain MRI is routine for many neurological diseases and conditions and relies on accurate segmentation of structures of interest. Deep learning-based segmentation approaches for brain MRI are gaining interest due to their self-learning and generalization ability over large amounts of data. As the deep learning architectures are becoming more mature, they gradually outperform previous state-of-the-art classical machine learning algorithms. This review aims to provide an overview of current deep learning-based segmentation approaches for quantitative brain MRI. First we review the current deep learning architectures used for segmentation of anatomical brain structures and brain lesions. Next, the performance, speed, and properties of deep learning approaches are summarized and discussed. Finally, we provide a critical assessment of the current state and identify likely future developments and trends.

Deep learning for hybrid EEG-fNIRS brain–computer interface: application to motor imagery classification

NASA Astrophysics Data System (ADS)

Chiarelli, Antonio Maria; Croce, Pierpaolo; Merla, Arcangelo; Zappasodi, Filippo

2018-06-01

Objective. Brain–computer interface (BCI) refers to procedures that link the central nervous system to a device. BCI was historically performed using electroencephalography (EEG). In the last years, encouraging results were obtained by combining EEG with other neuroimaging technologies, such as functional near infrared spectroscopy (fNIRS). A crucial step of BCI is brain state classification from recorded signal features. Deep artificial neural networks (DNNs) recently reached unprecedented complex classification outcomes. These performances were achieved through increased computational power, efficient learning algorithms, valuable activation functions, and restricted or back-fed neurons connections. By expecting significant overall BCI performances, we investigated the capabilities of combining EEG and fNIRS recordings with state-of-the-art deep learning procedures. Approach. We performed a guided left and right hand motor imagery task on 15 subjects with a fixed classification response time of 1 s and overall experiment length of 10 min. Left versus right classification accuracy of a DNN in the multi-modal recording modality was estimated and it was compared to standalone EEG and fNIRS and other classifiers. Main results. At a group level we obtained significant increase in performance when considering multi-modal recordings and DNN classifier with synergistic effect. Significance. BCI performances can be significantly improved by employing multi-modal recordings that provide electrical and hemodynamic brain activity information, in combination with advanced non-linear deep learning classification procedures.

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

PubMed

Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

2018-04-01

Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

Ethics of the electrified mind: Defining issues and perspectives on the principled use of brain stimulation in medical research and clinical care

PubMed Central

Cabrera, Laura Y.; Evans, Emily L.; Hamilton, Roy H.

2013-01-01

In recent years, non-pharmacologic approaches to modifying human neural activity have gained increasing attention. One of these approaches is brain stimulation, which involves either the direct application of electrical current to structures in the nervous system or the indirect application of current by means of electromagnetic induction. Interventions that manipulate the brain have generally been regarded as having both the potential to alleviate devastating brain-related conditions and the capacity to create unforeseen and unwanted consequences. Hence, although brain stimulation techniques offer considerable benefits to society, they also raise a number of ethical concerns. In this paper we will address various dilemmas related to brain stimulation in the context of clinical practice and biomedical research. We will survey current work involving deep brain stimulation (DBS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). We will reflect upon relevant similarities and differences between them, and consider some potentially problematic issues that may arise within the framework of established principles of medical ethics: nonmaleficence and beneficence, autonomy, and justice. PMID:23733209

Phase dependent modulation of tremor amplitude in essential tremor through thalamic stimulation

PubMed Central

Cagnan, Hayriye; Brittain, John-Stuart; Little, Simon; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Joint, Carole; Fitzgerald, James; Green, Alexander L.; Aziz, Tipu

2013-01-01

High frequency deep brain stimulation of the thalamus can help ameliorate severe essential tremor. Here we explore how the efficacy, efficiency and selectivity of thalamic deep brain stimulation might be improved in this condition. We started from the hypothesis that the effects of electrical stimulation on essential tremor may be phase dependent, and that, in particular, there are tremor phases at which stimuli preferentially lead to a reduction in the amplitude of tremor. The latter could be exploited to improve deep brain stimulation, particularly if tremor suppression could be reinforced by cumulative effects. Accordingly, we stimulated 10 patients with essential tremor and thalamic electrodes, while recording tremor amplitude and phase. Stimulation near the postural tremor frequency entrained tremor. Tremor amplitude was also modulated depending on the phase at which stimulation pulses were delivered in the tremor cycle. Stimuli in one half of the tremor cycle reduced median tremor amplitude by ∼10%, while those in the opposite half of the tremor cycle increased tremor amplitude by a similar amount. At optimal phase alignment tremor suppression reached 27%. Moreover, tremor amplitude showed a non-linear increase in the degree of suppression with successive stimuli; tremor suppression was increased threefold if a stimulus was preceded by four stimuli with a similar phase relationship with respect to the tremor, suggesting cumulative, possibly plastic, effects. The present results pave the way for a stimulation system that tracks tremor phase to control when deep brain stimulation pulses are delivered to treat essential tremor. This would allow treatment effects to be maximized by focussing stimulation on the optimal phase for suppression and by ensuring that this is repeated over many cycles so as to harness cumulative effects. Such a system might potentially achieve tremor control with far less power demand and greater specificity than current high frequency stimulation approaches, and may lower the risk for tolerance and rebound. PMID:24038075

On-chip phase-change photonic memory and computing

NASA Astrophysics Data System (ADS)

Cheng, Zengguang; Ríos, Carlos; Youngblood, Nathan; Wright, C. David; Pernice, Wolfram H. P.; Bhaskaran, Harish

2017-08-01

The use of photonics in computing is a hot topic of interest, driven by the need for ever-increasing speed along with reduced power consumption. In existing computing architectures, photonic data storage would dramatically improve the performance by reducing latencies associated with electrical memories. At the same time, the rise of `big data' and `deep learning' is driving the quest for non-von Neumann and brain-inspired computing paradigms. To succeed in both aspects, we have demonstrated non-volatile multi-level photonic memory avoiding the von Neumann bottleneck in the existing computing paradigm and a photonic synapse resembling the biological synapses for brain-inspired computing using phase-change materials (Ge2Sb2Te5).

Rechargeable internal neural stimulators--is there a problem with efficacy?

PubMed

Harries, Anwen M; Major, Shannon; Sandhu, Mandeep; Honey, Christopher R

2012-01-01

With the advent of rechargeable internal neural stimulators (rINS) for deep brain stimulation, our aim was to survey patient satisfaction and clinical efficacy in an early cohort of patients receiving this new technology. This is an observational study on nine patients with rINS. All patients had initially received non-rechargeable INS with established efficacy of their deep brain stimulation system for either dystonia or pain. Patient satisfaction and efficacy with their rINS were established by completion of a questionnaire, a quality of life assessment (SF-36), and calculation of the total electrical energy delivered (TEED) by the rINS. A reduction in efficacy of their rINS was noticed in 22% of patients. In 78% of patients, there was a problem with recharging their rINS because of poor contact. Two patients (22%) felt that recharging the rINS interfered with their lives and it was a daily reminder that they had a deep brain stimulator system in situ. Eight out of nine patients (89%), however, would recommend to other patients to have an rINS. Most patients were happy with their rechargeable internal neural stimulator. A reduction in efficacy was noticed in 22% of patients, which is similar to the proportion of patients noticing a reduction in efficacy when replacing with a non-rechargeable system. Thus, all patients require close monitoring post-replacement of rINS, in case possible adjustment of parameters is required. © 2011 International Neuromodulation Society.

Somatic Treatments for Mood Disorders

PubMed Central

Rosa, Moacyr A; Lisanby, Sarah H

2012-01-01

Somatic treatments for mood disorders represent a class of interventions available either as a stand-alone option, or in combination with psychopharmacology and/or psychotherapy. Here, we review the currently available techniques, including those already in clinical use and those still under research. Techniques are grouped into the following categories: (1) seizure therapies, including electroconvulsive therapy and magnetic seizure therapy, (2) noninvasive techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and cranial electric stimulation, (3) surgical approaches, including vagus nerve stimulation, epidural electrical stimulation, and deep brain stimulation, and (4) technologies on the horizon. Additionally, we discuss novel approaches to the optimization of each treatment, and new techniques that are under active investigation. PMID:21976043

Material and physical model for evaluation of deep brain activity contribution to EEG recordings

NASA Astrophysics Data System (ADS)

Ye, Yan; Li, Xiaoping; Wu, Tiecheng; Li, Zhe; Xie, Wenwen

2015-12-01

Deep brain activity is conventionally recorded with surgical implantation of electrodes. During the neurosurgery, brain tissue damage and the consequent side effects to patients are inevitably incurred. In order to eliminate undesired risks, we propose that deep brain activity should be measured using the noninvasive scalp electroencephalography (EEG) technique. However, the deeper the neuronal activity is located, the noisier the corresponding scalp EEG signals are. Thus, the present study aims to evaluate whether deep brain activity could be observed from EEG recordings. In the experiment, a three-layer cylindrical head model was constructed to mimic a human head. A single dipole source (sine wave, 10 Hz, altering amplitudes) was embedded inside the model to simulate neuronal activity. When the dipole source was activated, surface potential was measured via electrodes attached on the top surface of the model and raw data were recorded for signal analysis. Results show that the dipole source activity positioned at 66 mm depth in the model, equivalent to the depth of deep brain structures, is clearly observed from surface potential recordings. Therefore, it is highly possible that deep brain activity could be observed from EEG recordings and deep brain activity could be measured using the noninvasive scalp EEG technique.

Microfiberoptic fluorescence photobleaching reveals size-dependent macromolecule diffusion in extracellular space deep in brain.

PubMed

Zador, Zsolt; Magzoub, Mazin; Jin, Songwan; Manley, Geoffrey T; Papadopoulos, Marios C; Verkman, A S

2008-03-01

Diffusion in brain extracellular space (ECS) is important for nonsynaptic intercellular communication, extracellular ionic buffering, and delivery of drugs and metabolites. We measured macromolecular diffusion in normally light-inaccessible regions of mouse brain by microfiberoptic epifluorescence photobleaching, in which a fiberoptic with a micron-size tip is introduced deep in brain tissue. In brain cortex, the diffusion of a noninteracting molecule [fluorescein isothiocyanate (FITC)-dextran, 70 kDa] was slowed 4.5 +/- 0.5-fold compared with its diffusion in water (D(o)/D), and was depth-independent down to 800 microm from the brain surface. Diffusion was significantly accelerated (D(o)/D of 2.9+/-0.3) in mice lacking the glial water channel aquaporin-4. FITC-dextran diffusion varied greatly in different regions of brain, with D(o)/D of 3.5 +/- 0.3 in hippocampus and 7.4 +/- 0.3 in thalamus. Remarkably, D(o)/D in deep brain was strongly dependent on solute size, whereas diffusion in cortex changed little with solute size. Mathematical modeling of ECS diffusion required nonuniform ECS dimensions in deep brain, which we call "heterometricity," to account for the size-dependent diffusion. Our results provide the first data on molecular diffusion in ECS deep in brain in vivo and demonstrate previously unrecognized hindrance and heterometricity for diffusion of large macromolecules in deep brain.

Impact of cysts during radiofrequency lesioning in deep brain structures—a simulation and in vitro study

NASA Astrophysics Data System (ADS)

Johansson, Johannes D.; Loyd, Dan; Wårdell, Karin; Wren, Joakim

2007-06-01

Radiofrequency lesioning of nuclei in the thalamus or the basal ganglia can be used to reduce symptoms caused by e.g. movement disorders such as Parkinson's disease. Enlarged cavities containing cerebrospinal fluid (CSF) are commonly present in the basal ganglia and tend to increase in size and number with age. Since the cavities have different electrical and thermal properties compared with brain tissue, it is likely that they can affect the lesioning process and thereby the treatment outcome. Computer simulations using the finite element method and in vitro experiments have been used to investigate the impact of cysts on lesions' size and shape. Simulations of the electric current and temperature distributions as well as convective movements have been conducted for various sizes, shapes and locations of the cysts as well as different target temperatures. Circulation of the CSF caused by the heating was found to spread heat effectively and the higher electric conductivity of the CSF increased heating of the cyst. These two effects were together able to greatly alter the resulting lesion size and shape when the cyst was in contact with the electrode tip. Similar results were obtained for the experiments.

Effects of high-frequency stimulation of the internal pallidal segment on neuronal activity in the thalamus in parkinsonian monkeys

PubMed Central

Kammermeier, Stefan; Pittard, Damien; Hamada, Ikuma

2016-01-01

Deep brain stimulation of the internal globus pallidus (GPi) is a major treatment for advanced Parkinson's disease. The effects of this intervention on electrical activity patterns in targets of GPi output, specifically in the thalamus, are poorly understood. The experiments described here examined these effects using electrophysiological recordings in two Rhesus monkeys rendered moderately parkinsonian through treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), after sampling control data in the same animals. Analysis of spontaneous spiking activity of neurons in the basal ganglia-receiving areas of the ventral thalamus showed that MPTP-induced parkinsonism is associated with a reduction of firing rates of segments of the data that contained neither bursts nor decelerations, and with increased burst firing. Spectral analyses revealed an increase of power in the 3- to 13-Hz band and a reduction in the γ-range in the spiking activity of these neurons. Electrical stimulation of the ventrolateral motor territory of GPi with macroelectrodes, mimicking deep brain stimulation in parkinsonian patients (bipolar electrodes, 0.5 mm intercontact distance, biphasic stimuli, 120 Hz, 100 μs/phase, 200 μA), had antiparkinsonian effects. The stimulation markedly reduced oscillations in thalamic firing in the 13- to 30-Hz range and uncoupled the spiking activity of recorded neurons from simultaneously recorded local field potential (LFP) activity. These results confirm that oscillatory and nonoscillatory characteristics of spontaneous activity in the basal ganglia receiving ventral thalamus are altered in MPTP-induced parkinsonism. Electrical stimulation of GPi did not entrain thalamic activity but changed oscillatory activity in the ventral thalamus and altered the relationship between spikes and simultaneously recorded LFPs. PMID:27683881

Mechanisms for pattern specificity of deep-brain stimulation in Parkinson’s disease

PubMed Central

Mato, Germán; Dellavale, Damián

2017-01-01

Deep brain stimulation (DBS) has become a widely used technique for treating advanced stages of neurological and psychiatric illness. In the case of motor disorders related to basal ganglia (BG) dysfunction, several mechanisms of action for the DBS therapy have been identified which might be involved simultaneously or in sequence. However, the identification of a common key mechanism underlying the clinical relevant DBS configurations has remained elusive due to the inherent complexity related to the interaction between the electrical stimulation and the neural tissue, and the intricate circuital structure of the BG-thalamocortical network. In this work, it is shown that the clinically relevant range for both, the frequency and intensity of the electrical stimulation pattern, is an emergent property of the BG anatomy at the system-level that can be addressed using mean-field descriptive models of the BG network. Moreover, it is shown that the activity resetting mechanism elicited by electrical stimulation provides a natural explanation to the ineffectiveness of irregular (i.e., aperiodic) stimulation patterns, which has been commonly observed in previously reported pathophysiology models of Parkinson’s disease. Using analytical and numerical techniques, these results have been reproduced in both cases: 1) a reduced mean-field model that can be thought as an elementary building block capable to capture the underlying fundamentals of the relevant loops constituting the BG-thalamocortical network, and 2) a detailed model constituted by the direct and hyperdirect loops including one-dimensional spatial structure of the BG nuclei. We found that the optimal ranges for the essential parameters of the stimulation patterns can be understood without taking into account biophysical details of the relevant structures. PMID:28813460

Sensor probes and phantoms for advanced transcranial magnetic stimulation system developments

NASA Astrophysics Data System (ADS)

Meng, Qinglei; Patel, Prashil; Trivedi, Sudhir; Du, Xiaoming; Hong, Elliot; Choa, Fow-Sen

2015-05-01

Transcranial magnetic stimulation (TMS) has become one of the most widely used noninvasive method for brain tissue stimulation and has been used as a treatment tool for various neurological and psychiatric disorders including migraine, stroke, Parkinson's disease, dystonia, tinnitus and depression. In the process of developing advanced TMS deep brain stimulation tools, we need first to develop field measurement devices like sensory probes and brain phantoms, which can be used to calibrate the TMS systems. Currently there are commercially available DC magnetic or electric filed measurement sensors, but there is no instrument to measure transient fields. In our study, we used a commercial figure-8 shaped TMS coil to generate transient magnetic field and followed induced field and current. The coil was driven by power amplified signal from a pulse generator with tunable pulse rate, amplitude, and duration. In order to obtain a 3D plot of induced vector electric field, many types of probes were designed to detect single component of electric-field vectors along x, y and z axis in the space around TMS coil. We found that resistor probes has an optimized signal-to-noise ratio (SNR) near 3k ohm but it signal output is too weak compared with other techniques. We also found that inductor probes can have very high output for Curl E measurement, but it is not the E-field distribution we are interested in. Probes with electrical wire wrapped around iron coil can directly measure induced E-field with high sensitivity, which matched computer simulation results.

Inferring deep-brain activity from cortical activity using functional near-infrared spectroscopy

PubMed Central

Liu, Ning; Cui, Xu; Bryant, Daniel M.; Glover, Gary H.; Reiss, Allan L.

2015-01-01

Functional near-infrared spectroscopy (fNIRS) is an increasingly popular technology for studying brain function because it is non-invasive, non-irradiating and relatively inexpensive. Further, fNIRS potentially allows measurement of hemodynamic activity with high temporal resolution (milliseconds) and in naturalistic settings. However, in comparison with other imaging modalities, namely fMRI, fNIRS has a significant drawback: limited sensitivity to hemodynamic changes in deep-brain regions. To overcome this limitation, we developed a computational method to infer deep-brain activity using fNIRS measurements of cortical activity. Using simultaneous fNIRS and fMRI, we measured brain activity in 17 participants as they completed three cognitive tasks. A support vector regression (SVR) learning algorithm was used to predict activity in twelve deep-brain regions using information from surface fNIRS measurements. We compared these predictions against actual fMRI-measured activity using Pearson’s correlation to quantify prediction performance. To provide a benchmark for comparison, we also used fMRI measurements of cortical activity to infer deep-brain activity. When using fMRI-measured activity from the entire cortex, we were able to predict deep-brain activity in the fusiform cortex with an average correlation coefficient of 0.80 and in all deep-brain regions with an average correlation coefficient of 0.67. The top 15% of predictions using fNIRS signal achieved an accuracy of 0.7. To our knowledge, this study is the first to investigate the feasibility of using cortical activity to infer deep-brain activity. This new method has the potential to extend fNIRS applications in cognitive and clinical neuroscience research. PMID:25798327

Monitoring Dopamine ex Vivo during Electrical Stimulation Using Liquid-Microjunction Surface Sampling.

PubMed

Gill, Emily L; Marks, Megan; Yost, Richard A; Vedam-Mai, Vinata; Garrett, Timothy J

2017-12-19

Liquid-microjunction surface sampling (LMJ-SS) is an ambient ionization technique based on the continuous flow of solvent using an in situ microextraction device in which solvent moves through the probe, drawing in the analytes in preparation for ionization using an electrospray ionization source. However, unlike traditional mass spectrometry (MS) techniques, it operates under ambient pressure and requires no sample preparation, thereby making it ideal for rapid sampling of thicker tissue sections for electrophysiological and other neuroscientific research studies. Studies interrogating neural synapses, or a specific neural circuit, typically employ thick, ex vivo tissue sections maintained under near-physiological conditions to preserve tissue viability and maintain the neural networks. Deep brain stimulation (DBS) is a surgical procedure used to treat the neurological symptoms that are associated with certain neurodegenerative and neuropsychiatric diseases. Parkinson's disease (PD) is a neurological disorder which is commonly treated with DBS therapy. PD is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta portion of the brain. Here, we demonstrate that the LMJ-SS methodology can provide a platform for ex vivo analysis of the brain during electrical stimulation, such as DBS. We employ LMJ-SS in the ex vivo analysis of mouse brain tissue for monitoring dopamine during electrical stimulation of the striatum region. The mouse brain tissue was sectioned fresh post sacrifice and maintained in artificial cerebrospinal fluid to create near-physiological conditions before direct sampling using LMJ-SS. A selection of metabolites, including time-sensitive metabolites involved in energy regulation in the brain, were identified using standards, and the mass spectral database mzCloud was used to assess the feasibility of the methodology. Thereafter, the intensity of m/z 154 corresponding to protonated dopamine was monitored before and after electrical stimulation of the striatum region, showing an increase in signal directly following a stimulation event. Dopamine is the key neurotransmitter implicated in PD, and although electrochemical detectors have shown such increases in dopamine post-DBS, this is the first study to do so using MS methodologies.

Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial.

PubMed

Weaver, Frances M; Follett, Kenneth; Stern, Matthew; Hur, Kwan; Harris, Crystal; Marks, William J; Rothlind, Johannes; Sagher, Oren; Reda, Domenic; Moy, Claudia S; Pahwa, Rajesh; Burchiel, Kim; Hogarth, Penelope; Lai, Eugene C; Duda, John E; Holloway, Kathryn; Samii, Ali; Horn, Stacy; Bronstein, Jeff; Stoner, Gatana; Heemskerk, Jill; Huang, Grant D

2009-01-07

Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients. To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy. Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (< 70 years vs > or = 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage > or = 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006. Bilateral deep brain stimulation of the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Patients receiving best medical therapy (n = 134) were actively managed by movement disorder neurologists. The primary outcome was time spent in the "on" state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events. Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P < .001). Motor function improved significantly (P < .001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (> or = 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P < .001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P < .001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage. In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events. clinicaltrials.gov Identifier: NCT00056563.

Optimizing a Rodent Model of Parkinson's Disease for Exploring the Effects and Mechanisms of Deep Brain Stimulation

PubMed Central

Nowak, Karl; Mix, Eilhard; Gimsa, Jan; Strauss, Ulf; Sriperumbudur, Kiran Kumar; Benecke, Reiner; Gimsa, Ulrike

2011-01-01

Deep brain stimulation (DBS) has become a treatment for a growing number of neurological and psychiatric disorders, especially for therapy-refractory Parkinson's disease (PD). However, not all of the symptoms of PD are sufficiently improved in all patients, and side effects may occur. Further progress depends on a deeper insight into the mechanisms of action of DBS in the context of disturbed brain circuits. For this, optimized animal models have to be developed. We review not only charge transfer mechanisms at the electrode/tissue interface and strategies to increase the stimulation's energy-efficiency but also the electrochemical, electrophysiological, biochemical and functional effects of DBS. We introduce a hemi-Parkinsonian rat model for long-term experiments with chronically instrumented rats carrying a backpack stimulator and implanted platinum/iridium electrodes. This model is suitable for (1) elucidating the electrochemical processes at the electrode/tissue interface, (2) analyzing the molecular, cellular and behavioral stimulation effects, (3) testing new target regions for DBS, (4) screening for potential neuroprotective DBS effects, and (5) improving the efficacy and safety of the method. An outlook is given on further developments of experimental DBS, including the use of transgenic animals and the testing of closed-loop systems for the direct on-demand application of electric stimulation. PMID:21603182

Resting state functional MRI in Parkinson’s disease: the impact of deep brain stimulation on ‘effective’ connectivity

PubMed Central

Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl

2014-01-01

Depleted of dopamine, the dynamics of the parkinsonian brain impact on both ‘action’ and ‘resting’ motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the ‘effective’ connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network—disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses. PMID:24566670

Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.

PubMed

Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom

2014-04-01

Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.

Triple Halo Coil: Development and Comparison with Other TMS Coils

NASA Astrophysics Data System (ADS)

Rastogi, Priyam; Hadimani, Ravi; Jiles, David

Transcranial Magnetic Stimulation (TMS) is a non-invasive stimulation technique that can be used for the treatment of various neurological disorders such as Parkinson's Disease, PTSD, TBI and anxiety by regulating synaptic activity. TMS is FDA approved for the treatment of major depressive disorder. There is a critical need to develop deep TMS coils that can stimulate deeper regions of the brain without excessively stimulating the cortex in order to provide an alternative to surgical methods. We have developed a novel multi-coil configuration called ``Triple Halo Coil'' (THC) that can stimulate deep brain regions. Investigation of induced electric and magnetic field in these regions have been achieved by computer modelling. Comparison of the results due to THC configuration have been conducted with other TMS coils such as ``Halo Coil'', circular coil and ``Figure of Eight'' coil. There was an improvement of more than 15 times in the strength of magnetic field, induced by THC configuration at 10 cm below the vertex of the head when compared with the ``Figure of Eight'' coil alone. Carver Charitable Trust.

A tripolar current-steering stimulator ASIC for field shaping in deep brain stimulation.

PubMed

Valente, Virgilio; Demosthenous, Andreas; Bayford, Richard

2012-06-01

A significant problem with clinical deep brain stimulation (DBS) is the high variability of its efficacy and the frequency of side effects, related to the spreading of current beyond the anatomical target area. This is the result of the lack of control that current DBS systems offer on the shaping of the electric potential distribution around the electrode. This paper presents a stimulator ASIC with a tripolar current-steering output stage, aiming at achieving more selectivity and field shaping than current DBS systems. The ASIC was fabricated in a 0.35-μ m CMOS technology occupying a core area of 0.71 mm(2). It consists of three current sourcing/sinking channels. It is capable of generating square and exponential-decay biphasic current pulses with five different time constants up to 28 ms and delivering up to 1.85 mA of cathodic current, in steps of 4 μA, from a 12 V power supply. Field shaping was validated by mapping the potential distribution when injecting current pulses through a multicontact DBS electrode in saline.

State of the Art: Novel Applications for Cortical Stimulation.

PubMed

De Ridder, Dirk; Perera, Sanjaya; Vanneste, Sven

2017-04-01

Electrical stimulation via implanted electrodes that overlie the cortex of the brain is an upcoming neurosurgical technique that was hindered for a long time by insufficient knowledge of how the brain functions in a dynamic, physiological, and pathological way, as well as by technological limitations of the implantable stimulation devices. This paper provides an overview of cortex stimulation via implantable devices and introduces future possibilities to improve cortex stimulation. Cortex stimulation was initially used preoperatively as a technique to localize functions in the brain and only later evolved into a treatment technique. It was first used for pain, but more recently a multitude of pathologies are being targeted by cortex stimulation. These disorders are being treated by stimulating different cortical areas of the brain. Risks and complications are essentially similar to those related to deep brain stimulation and predominantly include haemorrhage, seizures, infection, and hardware failures. For cortex stimulation to fully mature, further technological development is required to predict its outcomes and improve stimulation designs. This includes the development of network science-based functional connectivity approaches, genetic analyses, development of navigated high definition transcranial alternating current stimulation, and development of pseudorandom stimulation designs for preventing habituation. In conclusion, cortex stimulation is a nascent but very promising approach to treating a variety of diseases, but requires further technological development for predicting outcomes, such as network science based functional connectivity approaches, genetic analyses, development of navigated transcranial electrical stimulation, and development of pseudorandom stimulation designs for preventing habituation. © 2017 International Neuromodulation Society.

Syringe Port: A Convenient, Safe, and Cost-Effective Tubular Retractor for Transportal Removal of Deep-Seated Lesions of the Brain.

PubMed

Singh, Harnarayan; Patir, Rana; Vaishya, Sandeep; Miglani, Rahul; Kaur, Amandeep

2018-06-01

Minimally invasive transportal resection of deep intracranial lesions has become a widely accepted surgical technique. Many disposable, mountable port systems are available in the market for this purpose, like the ViewSite Brain Access System. The objective of this study was to find a cost-effective substitute for these systems. Deep-seated brain lesions were treated with a port system made from disposable syringes. The syringe port could be inserted through minicraniotomies placed and planned with navigation. All deep-seated lesions like ventricular tumours, colloid cysts, deep-seated gliomas, and basal ganglia hemorrhages were treated with this syringe port system and evaluated for safety, operative site hematomas, and blood loss. 62 patients were operated on during the study period from January 2015 to July 2017, using this innovative syringe port system for deep-seated lesions of the brain. No operative site hematoma or contusions were seen along the port entry site and tract. Syringe port is a cost-effective and safe alternative to the costly disposable brain port systems, especially for neurosurgical setups in developing countries for minimally invasive transportal resection of deep brain lesions. Copyright © 2018 Elsevier Inc. All rights reserved.

From miracle to reconciliation: a hermeneutic phenomenological study exploring the experience of living with Parkinson's disease following deep brain stimulation.

PubMed

Haahr, Anita; Kirkevold, Marit; Hall, Elisabeth O C; Ostergaard, Karen

2010-10-01

Deep Brain Stimulation for Parkinson's disease is a promising treatment for patients who can no longer be treated satisfactorily with L-dopa. Deep Brain Stimulation is known to relieve motor symptoms of Parkinson's disease and improve quality of life. Focusing on how patients experience life when treated with Deep Brain Stimulation can provide essential information on the process patients go through when receiving a treatment that alters the body and changes the illness trajectory. The aim of this study was to explore and describe the experience of living with Parkinson's disease when treated with Deep Brain Stimulation. The study was designed as a longitudinal study and data were gathered through qualitative in-depth interviews three times during the first year of treatment. Nine patients participated in the study. They were included when they had accepted treatment with Deep Brain Stimulation for Parkinson's disease. Data collection and data analysis were inspired by the hermeneutic phenomenological methodology of Van Manen. The treatment had a major impact on the body. Participants experienced great bodily changes and went through a process of adjustment in three phases during the first year of treatment with Deep Brain Stimulation. These stages were; being liberated: a kind of miracle, changes as a challenge: decline or opportunity and reconciliation: re-defining life with Parkinson's disease. The course of the process was unique for each participant, but dominant was that difficulties during the adjustment of stimulation and medication did affect the re-defining process. Patients go through a dramatic process of change following Deep Brain Stimulation. A changing body affects their entire lifeworld. Some adjust smoothly to changes while others are affected by loss of control, uncertainty and loss of everyday life as they knew it. These experiences affect the process of adjusting to life with Deep Brain Stimulation and re-define life with Parkinson's disease. It is of significant importance that health care professionals are aware of these dramatic changes in the patients' life and offer support during the adjustment process following Deep Brain Stimulation. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Roadmap on neurophotonics

NASA Astrophysics Data System (ADS)

Cho, Yong Ku; Zheng, Guoan; Augustine, George J.; Hochbaum, Daniel; Cohen, Adam; Knöpfel, Thomas; Pisanello, Ferruccio; Pavone, Francesco S.; Vellekoop, Ivo M.; Booth, Martin J.; Hu, Song; Zhu, Jiang; Chen, Zhongping; Hoshi, Yoko

2016-09-01

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken.

Roadmap on neurophotonics

PubMed Central

Cho, Yong Ku; Zheng, Guoan; Augustine, George J; Hochbaum, Daniel; Cohen, Adam; Knöpfel, Thomas; Pisanello, Ferruccio; Pavone, Francesco S; Vellekoop, Ivo M; Booth, Martin J; Hu, Song; Zhu, Jiang; Chen, Zhongping; Hoshi, Yoko

2017-01-01

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken. PMID:28386392

Electromagnetic Field Modeling of Transcranial Electric and Magnetic Stimulation: Targeting, Individualization, and Safety of Convulsive and Subconvulsive Applications

NASA Astrophysics Data System (ADS)

Deng, Zhi-De

The proliferation of noninvasive transcranial electric and magnetic brain stimulation techniques and applications in recent years has led to important insights into brain function and pathophysiology of brain-based disorders. Transcranial electric and magnetic stimulation encompasses a wide spectrum of methods that have developed into therapeutic interventions for a variety of neurological and psychiatric disorders. Although these methods are at different stages of development, the physical principle underlying these techniques is the similar. Namely, an electromagnetic field is induced in the brain either via current injection through scalp electrodes or via electromagnetic induction. The induced electric field modulates the neuronal transmembrane potentials and, thereby, neuronal excitability or activity. Therefore, knowledge of the induced electric field distribution is key in the design and interpretation of basic research and clinical studies. This work aims to delineate the fundamental physical limitations, tradeoffs, and technological feasibility constraints associated with transcranial electric and magnetic stimulation, in order to inform the development of technologies that deliver safer, and more spatially, temporally, and patient specific stimulation. Part I of this dissertation expounds on the issue of spatial targeting of the electric field. Contrasting electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) configurations that differ markedly in efficacy, side effects, and seizure induction efficiency could advance our understanding of the principles linking treatment parameters and therapeutic outcome and could provide a means of testing hypotheses of the mechanisms of therapeutic action. Using the finite element method, we systematically compare the electric field characteristics of existing forms of ECT and MST. We introduce a method of incorporating a modality-specific neural activation threshold in the electric field models that can inform dosage requirements in convulsive therapies. Our results indicate that the MST electric field is more focal and more confined to the superficial cortex compared to ECT. Further, the conventional ECT current amplitude is much higher than necessary for seizure induction. One of the factors important to clinical outcome is seizure expression. However, it is unknown how the induced electric field is related to seizure onset and propagation. In this work, we explore the effect of the electric field distribution on the quantitative ictal electroencephalography and current source density in ECT and MST. We further demonstrate how the ECT electrode shape, size, spacing, and current can be manipulated to yield more precise control of the induced electric field. If desirable, ECT can be made as focal as MST while using simpler stimulation equipment. Next, we demonstrate how the electric field induced by transcranial magnetic stimulation (TMS) can be controlled. We present the most comprehensive comparison of TMS coil electric field penetration and focality to date. The electric field distributions of more than 50 TMS coils were simulated. We show that TMS coils differ markedly in their electric field characteristics, but they all are subject to a consistent depth-focality tradeoff. Specifically, the ability to directly stimulate deeper brain structures is obtained at the expense of inducing wider electric field spread. Figure-8 type coils are fundamentally more focal compared to circular type coils. Understanding the depth-focality tradeoff can help researchers and clinicians to appropriately select coils and interpret TMS studies. This work also enables the development of novel TMS coils with electronically switchable active and sham modes as well as for deep TMS. Design considerations of these coils are extensively discussed. Part II of the dissertation aims to quantify the effect of individual, sex, and age differences in head geometry and conductivity on the induced neural stimulation strength and focality of ECT and MST. Across and within ECT studies, there is marked unexplained variability in seizure threshold and clinical outcomes. It is not known to what extent the age and sex effects on seizure threshold are mediated by interindividual variation in neural excitability and/or anatomy of the head. Addressing this question, we examine the effect on ECT and MST induced field characteristics of the variability in head diameter, scalp and skull thicknesses and conductivities, as well as brain volume, in a range of values that are representative of the patient population. Variations in the local tissue properties such as scalp and skull thickness and conductivity affect the existing ECT configurations more than MST. On the other hand, the existing MST coil configurations show greater sensitivity to head diameter variation compared to ECT. Due to the high focality of MST compared to ECT, the stimulated brain volume in MST is more sensitive to variation in tissue layer thicknesses. We further demonstrate how individualization of the stimulus pulse current amplitude, which is not presently done in ECT or MST, can be used as a means of compensating for interindividual anatomical variability, which could lead to better and more consistent clinical outcomes. Part III of the dissertation aims to systemically investigate, both computationally and experimentally, the safety of TMS and ECT in patients with a deep-brain stimulation system, and propose safety guidelines for the dual-device therapy. We showed that the induction of significant voltages in the subcutaneous leads in the scalp during TMS could result in unintended and potentially dangerous levels of electrical currents in the DBS electrode contacts. When applying ECT in patients with intracranial implants, we showed that there is an increase in the electric field strength in the brain due to conduction through the burr holes, especially when the burr holes are not fitted with nonconductive caps. Safety concerns presently limit the access of patients with intracranial electronic devices to therapies involving transcranial stimulation technology, which may preclude them from obtaining appropriate medical treatments. Gaining better understanding of the interactions between transcranial and implanted stimulation devices will demarcate significant safety risks from benign interactions, and will provide recommendations for reducing risk, thus enhancing the patient's therapeutic options.

Feasibility of Using Linearly Polarized Rotating Birdcage Transmitters and Close-Fitting Receive Arrays in MRI to Reduce SAR in the Vicinity of Deep Brain Simulation Implants

PubMed Central

Golestanirad, Laleh; Keil, Boris; Angelone, Leonardo M.; Bonmassar, Giorgio; Mareyam, Azma; Wald, Lawrence L.

2016-01-01

Purpose MRI of patients with deep brain stimulation (DBS) implants is strictly limited due to safety concerns, including high levels of local specific absorption rate (SAR) of radiofrequency (RF) fields near the implant and related RF-induced heating. This study demonstrates the feasibility of using a rotating linearly polarized birdcage transmitter and a 32-channel close-fit receive array to significantly reduce local SAR in MRI of DBS patients. Methods Electromagnetic simulations and phantom experiments were performed with generic DBS lead geometries and implantation paths. The technique was based on mechanically rotating a linear birdcage transmitter to align its zero electric-field region with the implant while using a close-fit receive array to significantly increase signal to noise ratio of the images. Results It was found that the zero electric-field region of the transmitter is thick enough at 1.5 Tesla to encompass DBS lead trajectories with wire segments that were up to 30 degrees out of plane, as well as leads with looped segments. Moreover, SAR reduction was not sensitive to tissue properties, and insertion of a close-fit 32-channel receive array did not degrade the SAR reduction performance. Conclusion The ensemble of rotating linear birdcage and 32-channel close-fit receive array introduces a promising technology for future improvement of imaging in patients with DBS implants. PMID:27059266

Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report.

PubMed

Themistocleous, Marios S; Boviatsis, Efstathios J; Stavrinou, Lampis C; Stathis, Pantelis; Sakas, Damianos E

2011-06-29

The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson's disease.

PubMed

Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir; Brown, Peter

2016-05-01

Chronic dopamine depletion in Parkinson's disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus-cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the possibility that cortical connectivity with the subthalamic nucleus in the high and low beta bands may reflect coupling mediated predominantly by the hyperdirect and indirect pathways to subthalamic nucleus, respectively, and that subthalamic nucleus deep brain stimulation predominantly suppresses the former. Yet only the change in strength of local subthalamic nucleus oscillations correlates with the degree of improvement during deep brain stimulation, compatible with the current view that a strengthened hyperdirect pathway is a prerequisite for locally generated beta activity but that it is the severity of the latter that may determine or index motor impairment. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Capacitive Feedthroughs for Medical Implants

PubMed Central

Grob, Sven; Tass, Peter A.; Hauptmann, Christian

2016-01-01

Important technological advances in the last decades paved the road to a great success story for electrically stimulating medical implants, including cochlear implants or implants for deep brain stimulation. However, there are still many challenges in reducing side effects and improving functionality and comfort for the patient. Two of the main challenges are the wish for smaller implants on one hand, and the demand for more stimulation channels on the other hand. But these two aims lead to a conflict of interests. This paper presents a novel design for an electrical feedthrough, the so called capacitive feedthrough, which allows both reducing the size, and increasing the number of included channels. Capacitive feedthroughs combine the functionality of a coupling capacitor and an electrical feedthrough within one and the same structure. The paper also discusses the progress and the challenges of the first produced demonstrators. The concept bears a high potential in improving current feedthrough technology, and could be applied on all kinds of electrical medical implants, even if its implementation might be challenging. PMID:27660602

Capacitive Feedthroughs for Medical Implants.

PubMed

Grob, Sven; Tass, Peter A; Hauptmann, Christian

2016-01-01

Important technological advances in the last decades paved the road to a great success story for electrically stimulating medical implants, including cochlear implants or implants for deep brain stimulation. However, there are still many challenges in reducing side effects and improving functionality and comfort for the patient. Two of the main challenges are the wish for smaller implants on one hand, and the demand for more stimulation channels on the other hand. But these two aims lead to a conflict of interests. This paper presents a novel design for an electrical feedthrough, the so called capacitive feedthrough, which allows both reducing the size, and increasing the number of included channels. Capacitive feedthroughs combine the functionality of a coupling capacitor and an electrical feedthrough within one and the same structure. The paper also discusses the progress and the challenges of the first produced demonstrators. The concept bears a high potential in improving current feedthrough technology, and could be applied on all kinds of electrical medical implants, even if its implementation might be challenging.

A microprobe for parallel optical and electrical recordings from single neurons in vivo.

PubMed

LeChasseur, Yoan; Dufour, Suzie; Lavertu, Guillaume; Bories, Cyril; Deschênes, Martin; Vallée, Réal; De Koninck, Yves

2011-04-01

Recording electrical activity from identified neurons in intact tissue is key to understanding their role in information processing. Recent fluorescence labeling techniques have opened new possibilities to combine electrophysiological recording with optical detection of individual neurons deep in brain tissue. For this purpose we developed dual-core fiberoptics-based microprobes, with an optical core to locally excite and collect fluorescence, and an electrolyte-filled hollow core for extracellular single unit electrophysiology. This design provides microprobes with tips < 10 μm, enabling analyses with single-cell optical resolution. We demonstrate combined electrical and optical detection of single fluorescent neurons in rats and mice. We combined electrical recordings and optical Ca²(+) measurements from single thalamic relay neurons in rats, and achieved detection and activation of single channelrhodopsin-expressing neurons in Thy1::ChR2-YFP transgenic mice. The microprobe expands possibilities for in vivo electrophysiological recording, providing parallel access to single-cell optical monitoring and control.

Long-term detection of Parkinsonian tremor activity from subthalamic nucleus local field potentials.

PubMed

Houston, Brady; Blumenfeld, Zack; Quinn, Emma; Bronte-Stewart, Helen; Chizeck, Howard

2015-01-01

Current deep brain stimulation paradigms deliver continuous stimulation to deep brain structures to ameliorate the symptoms of Parkinson's disease. This continuous stimulation has undesirable side effects and decreases the lifespan of the unit's battery, necessitating earlier replacement. A closed-loop deep brain stimulator that uses brain signals to determine when to deliver stimulation based on the occurrence of symptoms could potentially address these drawbacks of current technology. Attempts to detect Parkinsonian tremor using brain signals recorded during the implantation procedure have been successful. However, the ability of these methods to accurately detect tremor over extended periods of time is unknown. Here we use local field potentials recorded during a deep brain stimulation clinical follow-up visit 1 month after initial programming to build a tremor detection algorithm and use this algorithm to detect tremor in subsequent visits up to 8 months later. Using this method, we detected the occurrence of tremor with accuracies between 68-93%. These results demonstrate the potential of tremor detection methods for efficacious closed-loop deep brain stimulation over extended periods of time.

Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders

PubMed Central

2014-01-01

Background Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood. Results Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically. Conclusions Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models. PMID:24512669

Language context modulates reading route: an electrical neuroimaging study

PubMed Central

Buetler, Karin A.; de León Rodríguez, Diego; Laganaro, Marina; Müri, René; Spierer, Lucas; Annoni, Jean-Marie

2014-01-01

Introduction: The orthographic depth hypothesis (Katz and Feldman, 1983) posits that different reading routes are engaged depending on the type of grapheme/phoneme correspondence of the language being read. Shallow orthographies with consistent grapheme/phoneme correspondences favor encoding via non-lexical pathways, where each grapheme is sequentially mapped to its corresponding phoneme. In contrast, deep orthographies with inconsistent grapheme/phoneme correspondences favor lexical pathways, where phonemes are retrieved from specialized memory structures. This hypothesis, however, lacks compelling empirical support. The aim of the present study was to investigate the impact of orthographic depth on reading route selection using a within-subject design. Method: We presented the same pseudowords (PWs) to highly proficient bilinguals and manipulated the orthographic depth of PW reading by embedding them among two separated German or French language contexts, implicating respectively, shallow or deep orthography. High density electroencephalography was recorded during the task. Results: The topography of the ERPs to identical PWs differed 300–360 ms post-stimulus onset when the PWs were read in different orthographic depth context, indicating distinct brain networks engaged in reading during this time window. The brain sources underlying these topographic effects were located within left inferior frontal (German > French), parietal (French > German) and cingular areas (German > French). Conclusion: Reading in a shallow context favors non-lexical pathways, reflected in a stronger engagement of frontal phonological areas in the shallow versus the deep orthographic context. In contrast, reading PW in a deep orthographic context recruits less routine non-lexical pathways, reflected in a stronger engagement of visuo-attentional parietal areas in the deep versus shallow orthographic context. These collective results support a modulation of reading route by orthographic depth. PMID:24600377

Deep brain stimulation for people with Alzheimer's disease: Anticipating potential effects on the tripartite self.

PubMed

Viaña, John Noel M; Gilbert, Frederic

2018-01-01

Memory dysfunction and cognitive impairments due to Alzheimer's disease can affect the selfhood and identity of afflicted individuals, causing distress to both people with Alzheimer's disease and their caregivers. Recently, a number of case studies and clinical trials have been conducted to determine the potential of deep brain stimulation as a therapeutic modality for people with Alzheimer's disease. Some of these studies have shown that deep brain stimulation could induce flashbacks and stabilize or even improve memory. However, deep brain stimulation itself has also been attributed as a potential threat to identity and selfhood, especially when procedure-related adverse events arise. We anticipate potential effects of deep brain stimulation for people with Alzheimer's disease on selfhood, reconciling information from medical reports, psychological, and sociological investigations on the impacts of deep brain stimulation or Alzheimer's disease on selfhood. A tripartite model of the self that extends the scope of Rom Harré's and Steve Sabat's social constructionist framework was used. In this model, potential effects of deep brain stimulation for Alzheimer's disease on Self 1 or singularity through use of first-person indexicals, and gestures of self-reference, attribution, and recognition; Self 2 or past and present attributes, knowledge of these characteristics, and continuity of narrative identity; and Self 3 or the relational and social self are explored. The ethical implications of potential effects of deep brain stimulation for Alzheimer's disease on the tripartite self are then highlighted, focusing on adapting informed consent procedures and care provided throughout the trial to account for both positive and negative plausible effects on Self 1, Self 2, and Self 3.

Swept-source optical coherence tomography powered by a 1.3-μm vertical cavity surface emitting laser enables 2.3-mm-deep brain imaging in mice in vivo

NASA Astrophysics Data System (ADS)

Choi, Woo June; Wang, Ruikang K.

2015-10-01

We report noninvasive, in vivo optical imaging deep within a mouse brain by swept-source optical coherence tomography (SS-OCT), enabled by a 1.3-μm vertical cavity surface emitting laser (VCSEL). VCSEL SS-OCT offers a constant signal sensitivity of 105 dB throughout an entire depth of 4.25 mm in air, ensuring an extended usable imaging depth range of more than 2 mm in turbid biological tissue. Using this approach, we show deep brain imaging in mice with an open-skull cranial window preparation, revealing intact mouse brain anatomy from the superficial cerebral cortex to the deep hippocampus. VCSEL SS-OCT would be applicable to small animal studies for the investigation of deep tissue compartments in living brains where diseases such as dementia and tumor can take their toll.

Frameless Stereotactic Insertion of Viewsite Brain Access System with Microscope-Mounted Tracking Device for Resection of Deep Brain Lesions: Technical Report

PubMed Central

Chakraborty, Shamik; Lall, Rohan; Fanous, Andrew A; Boockvar, John; Langer, David J

2017-01-01

The surgical management of deep brain tumors is often challenging due to the limitations of stereotactic needle biopsies and the morbidity associated with transcortical approaches. We present a novel microscopic navigational technique utilizing the Viewsite Brain Access System (VBAS) (Vycor Medical, Boca Raton, FL, USA) for resection of a deep parietal periventricular high-grade glioma as well as another glioma and a cavernoma with no related morbidity. The approach utilized a navigational tracker mounted on a microscope, which was set to the desired trajectory and depth. It allowed gentle continuous insertion of the VBAS directly to a deep lesion under continuous microscopic visualization, increasing safety by obviating the need to look up from the microscope and thus avoiding loss of trajectory. This technique has broad value for the resection of a variety of deep brain lesions. PMID:28331774

Frameless Stereotactic Insertion of Viewsite Brain Access System with Microscope-Mounted Tracking Device for Resection of Deep Brain Lesions: Technical Report.

PubMed

White, Tim; Chakraborty, Shamik; Lall, Rohan; Fanous, Andrew A; Boockvar, John; Langer, David J

2017-02-04

The surgical management of deep brain tumors is often challenging due to the limitations of stereotactic needle biopsies and the morbidity associated with transcortical approaches. We present a novel microscopic navigational technique utilizing the Viewsite Brain Access System (VBAS) (Vycor Medical, Boca Raton, FL, USA) for resection of a deep parietal periventricular high-grade glioma as well as another glioma and a cavernoma with no related morbidity. The approach utilized a navigational tracker mounted on a microscope, which was set to the desired trajectory and depth. It allowed gentle continuous insertion of the VBAS directly to a deep lesion under continuous microscopic visualization, increasing safety by obviating the need to look up from the microscope and thus avoiding loss of trajectory. This technique has broad value for the resection of a variety of deep brain lesions.

A Stepwise Approach: Decreasing Infection in Deep Brain Stimulation for Childhood Dystonic Cerebral Palsy.

PubMed

Johans, Stephen J; Swong, Kevin N; Hofler, Ryan C; Anderson, Douglas E

2017-09-01

Dystonia is a movement disorder characterized by involuntary muscle contractions, which cause twisting movements or abnormal postures. Deep brain stimulation has been used to improve the quality of life for secondary dystonia caused by cerebral palsy. Despite being a viable treatment option for childhood dystonic cerebral palsy, deep brain stimulation is associated with a high rate of infection in children. The authors present a small series of patients with dystonic cerebral palsy who underwent a stepwise approach for bilateral globus pallidus interna deep brain stimulation placement in order to decrease the rate of infection. Four children with dystonic cerebral palsy who underwent a total of 13 surgical procedures (electrode and battery placement) were identified via a retrospective review. There were zero postoperative infections. Using a multistaged surgical plan for pediatric patients with dystonic cerebral palsy undergoing deep brain stimulation may help to reduce the risk of infection.

The human brain pacemaker: Synchronized infra-slow neurovascular coupling in patients undergoing non-pulsatile cardiopulmonary bypass.

PubMed

Zanatta, Paolo; Toffolo, Gianna Maria; Sartori, Elisa; Bet, Anna; Baldanzi, Fabrizio; Agarwal, Nivedita; Golanov, Eugene

2013-05-15

In non-pulsatile cardiopulmonary bypass surgery, middle cerebral artery blood flow velocity (BFV) is characterized by infra-slow oscillations of approximately 0.06Hz, which are paralleled by changes in total EEG power variability (EEG-PV), measured in 2s intervals. Since the origin of these BFV oscillations is not known, we explored their possible causative relationships with oscillations in EEG-PV at around 0.06Hz. We monitored 28 patients undergoing non-pulsatile cardiopulmonary bypass using transcranial Doppler sonography and scalp electroencephalography at two levels of anesthesia, deep (prevalence of burst suppression rhythm) and moderate (prevalence of theta rhythm). Under deep anesthesia, the EEG bursts suppression pattern was highly correlative with BFV oscillations. Hence, a detailed quantitative picture of the coupling between electrical brain activity and BFV was derived, both in deep and moderate anesthesia, via linear and non linear processing of EEG-PV and BFV signals, resorting to widely used measures of signal coupling such as frequency of oscillations, coherence, Granger causality and cross-approximate entropy. Results strongly suggest the existence of coupling between EEG-PV and BFV. In moderate anesthesia EEG-PV mean dominant frequency is similar to frequency of BFV oscillations (0.065±0.010Hz vs 0.045±0.019Hz); coherence between the two signals was significant in about 55% of subjects, and the Granger causality suggested an EEG-PV→BFV causal effect direction. The strength of the coupling increased with deepening anesthesia, as EEG-PV oscillations mean dominant frequency virtually coincided with the BFV peak frequency (0.062±0.017Hz vs 0.060±0.024Hz), and coherence became significant in a larger number (65%) of subjects. Cross-approximate entropy decreased significantly from moderate to deep anesthesia, indicating a higher level of synchrony between the two signals. Presence of a subcortical brain pacemaker that drives vascular infra-slow oscillations in the brain is proposed. These findings allow to suggest an original hypothesis explaining the mechanism underlying infra-slow neurovascular coupling. Copyright © 2013 Elsevier Inc. All rights reserved.

Electrical stimulation of the insular region attenuates nicotine-taking and nicotine-seeking behaviors.

PubMed

Pushparaj, Abhiram; Hamani, Clement; Yu, Wilson; Shin, Damian S; Kang, Bin; Nobrega, José N; Le Foll, Bernard

2013-03-01

Pharmacological inactivation of the granular insular cortex is able to block nicotine-taking and -seeking behaviors in rats. In this study, we explored the potential of modulating activity in the insular region using electrical stimulation. Animals were trained to self-administer nicotine (0.03 mg/kg per infusion) under a fixed ratio-5 (FR-5) schedule of reinforcement followed by a progressive ratio (PR) schedule. Evaluation of the effect of stimulation in the insular region was performed on nicotine self-administration under FR-5 and PR schedules, as well on reinstatement of nicotine-seeking behavior induced by nicotine-associated cues or nicotine-priming injections. The effect of stimulation was also examined in brain slices containing insular neurons. Stimulation significantly attenuated nicotine-taking, under both schedules of reinforcement, as well as nicotine-seeking behavior induced by cues and priming. These effects appear to be specific to nicotine-associated behaviors, as stimulation did not have any effect on food-taking behavior. They appear to be anatomically specific, as stimulation surrounding the insular region had no effect on behavior. Stimulation of brain slices containing the insular region was found to inactivate insular neurons. Our results suggest that deep brain stimulation to modulate insular activity should be further explored.

Innovations in deep brain stimulation methodology.

PubMed

Kühn, Andrea A; Volkmann, Jens

2017-01-01

Deep brain stimulation is a powerful clinical method for movement disorders that no longer respond satisfactorily to pharmacological management, but its progress has been hampered by stagnation in technological procedure solutions and device development. Recently, the combined research efforts of bioengineers, neuroscientists, and clinicians have helped to better understand the mechanisms of deep brain stimulation, and solutions for the translational roadblock are emerging. Here, we define the needs for methodological advances in deep brain stimulation from a neurophysiological perspective and describe technological solutions that are currently evaluated for near-term clinical application. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson’s disease

PubMed Central

Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir

2016-01-01

Abstract Chronic dopamine depletion in Parkinson’s disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus–cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the possibility that cortical connectivity with the subthalamic nucleus in the high and low beta bands may reflect coupling mediated predominantly by the hyperdirect and indirect pathways to subthalamic nucleus, respectively, and that subthalamic nucleus deep brain stimulation predominantly suppresses the former. Yet only the change in strength of local subthalamic nucleus oscillations correlates with the degree of improvement during deep brain stimulation, compatible with the current view that a strengthened hyperdirect pathway is a prerequisite for locally generated beta activity but that it is the severity of the latter that may determine or index motor impairment. PMID:27017189

Prediction and control of neural responses to pulsatile electrical stimulation

NASA Astrophysics Data System (ADS)

Campbell, Luke J.; Sly, David James; O'Leary, Stephen John

2012-04-01

This paper aims to predict and control the probability of firing of a neuron in response to pulsatile electrical stimulation of the type delivered by neural prostheses such as the cochlear implant, bionic eye or in deep brain stimulation. Using the cochlear implant as a model, we developed an efficient computational model that predicts the responses of auditory nerve fibers to electrical stimulation and evaluated the model's accuracy by comparing the model output with pooled responses from a group of guinea pig auditory nerve fibers. It was found that the model accurately predicted the changes in neural firing probability over time to constant and variable amplitude electrical pulse trains, including speech-derived signals, delivered at rates up to 889 pulses s-1. A simplified version of the model that did not incorporate adaptation was used to adaptively predict, within its limitations, the pulsatile electrical stimulus required to cause a desired response from neurons up to 250 pulses s-1. Future stimulation strategies for cochlear implants and other neural prostheses may be enhanced using similar models that account for the way that neural responses are altered by previous stimulation.

Electrical stimulation of the lateral habenula produces an inhibitory effect on sucrose self-administration.

PubMed

Friedman, Alexander; Lax, Elad; Dikshtein, Yahav; Abraham, Lital; Flaumenhaft, Yakov; Sudai, Einav; Ben-Tzion, Moshe; Yadid, Gal

2011-01-01

The lateral habenula (LHb) plays a role in prediction of negative reinforcement, punishment and aversive responses. In the current study, we examined the role that the LHb plays in regulation of negative reward responses and aversion. First, we tested the effect of intervention in LHb activity on sucrose reinforcing behavior. An electrode was implanted into the LHb and rats were trained to self-administer sucrose (20%; 16 days) until at least three days of stable performance were achieved (as represented by the number of active lever presses in self-administration cages). Rats subsequently received deep brain stimulation (DBS) of the LHb, which significantly reduced sucrose self-administration levels. In contrast, lesion of the LHb increased sucrose-seeking behavior, as demonstrated by a delayed extinction response to substitution of sucrose with water. Furthermore, in a modified non-rewarding conditioned-place-preference paradigm, DBS of the LHb led to aversion to the context associated with stimulation of this brain region. We postulate that electrical stimulation of the LHb attenuates positive reward-associated reinforcement by natural substances. Copyright © 2010 Elsevier Ltd. All rights reserved.

New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

PubMed

Radman, Thomas; Lisanby, Sarah H

2017-04-01

Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.

A novel combinational approach of microstimulation and bioluminescence imaging to study the mechanisms of action of cerebral electrical stimulation in mice

PubMed Central

Arsenault, Dany; Drouin-Ouellet, Janelle; Saint-Pierre, Martine; Petrou, Petros; Dubois, Marilyn; Kriz, Jasna; Barker, Roger A; Cicchetti, Antonio; Cicchetti, Francesca

2015-01-01

Key points We have developed a unique prototype to perform brain stimulation in mice. This system presents a number of advantages and new developments: 1) all stimulation parameters can be adjusted, 2) both positive and negative current pulses can be generated, guaranteeing electrically balanced stimulation regimen, 3) which can be produced with both low and high impedance electrodes, 4) the developed electrodes ensure localized stimulation and 5) can be used to stimulate and/or record brain potential and 6) in vivo recording of electric pulses allows the detection of defective electrodes (wire breakage or short circuits). This new micro-stimulator device further allows simultaneous live bioluminescence imaging of the mouse brain, enabling real time assessment of the impact of stimulation on cerebral tissue. The use of this novel tool in various transgenic mouse models of disease opens up a whole new range of possibilities in better understanding brain stimulation. Abstract Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique device to perform brain stimulation (BS) in mice and to address fundamental issues related to this methodology in the pre-clinical setting. This new microstimulator prototype was specifically designed to allow simultaneous live bioluminescence imaging of the mouse brain, allowing real time assessment of the impact of stimulation on cerebral tissue. We validated the authenticity of this tool in vivo by analysing the expression of toll-like receptor 2 (TLR2), corresponding to the microglial response, in the stimulated brain regions of TLR2-fluc-GFP transgenic mice, which we further corroborated with post-mortem analyses in these animals as well as in human brains of patients who underwent DBS to treat their Parkinson's disease. In the present study, we report on the development of the first BS device that allows for simultaneous live in vivo imaging in mice. This tool opens up a whole new range of possibilities that allow a better understanding of BS and how to optimize its effects through its use in murine models of disease. PMID:25653107

Uncovering the mechanism(s) of deep brain stimulation

NASA Astrophysics Data System (ADS)

Gang, Li; Chao, Yu; Ling, Lin; C-Y Lu, Stephen

2005-01-01

Deep brain stimulators, often called `pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

COMMUNICATION Designing a somatosensory neural prosthesis: percepts evoked by different patterns of thalamic stimulation

NASA Astrophysics Data System (ADS)

Heming, Ethan; Sanden, Andrew; Kiss, Zelma H. T.

2010-12-01

Although major advances have been made in the development of motor prostheses, fine motor control requires intuitive somatosensory feedback. Here we explored whether a thalamic site for a somatosensory neural prosthetic could provide natural somatic sensation to humans. Different patterns of electrical stimulation (obtained from thalamic spike trains) were applied in patients undergoing deep brain stimulation surgery. Changes in pattern produced different sensations, while preserving somatotopic representation. While most percepts were reported as 'unnatural', some stimulations produced more 'natural' sensations than others. However, the additional patterns did not elicit more 'natural' percepts than high-frequency (333 Hz) electrical stimulation. These features suggest that despite some limitations, the thalamus may be a feasible site for a somatosensory neural prosthesis and different stimulation patterns may be useful in its development.

Deep brain stimulation for severe treatment-resistant obsessive-compulsive disorder: An open-label case series.

PubMed

Farrand, Sarah; Evans, Andrew H; Mangelsdorf, Simone; Loi, Samantha M; Mocellin, Ramon; Borham, Adam; Bevilacqua, JoAnne; Blair-West, Scott; Walterfang, Mark A; Bittar, Richard G; Velakoulis, Dennis

2017-09-01

Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8-54 months). The sample included four females and three males, with a mean age of 46 years (range, 37-59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15-38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Deep brain stimulation was an effective treatment for obsessive-compulsive disorder in these highly selected patients. The extent of the response to deep brain stimulation varied between patients, as well as during the course of treatment for each patient. The results of this series are comparable with the literature, as well as having similar efficacy to ablative psychosurgery techniques such as capsulotomy and cingulotomy. Deep brain stimulation provides advantages over lesional psychosurgery but is more expensive and requires significant multidisciplinary input at all stages, pre- and post-operatively, ideally within a specialised tertiary clinical and/or academic centre. Ongoing research is required to better understand the neurobiological basis for obsessive-compulsive disorder and how this can be manipulated with deep brain stimulation to further improve the efficacy of this emerging treatment.

Sensing deep extreme environments: the receptor cell types, brain centers, and multi-layer neural packaging of hydrothermal vent endemic worms.

PubMed

Shigeno, Shuichi; Ogura, Atsushi; Mori, Tsukasa; Toyohara, Haruhiko; Yoshida, Takao; Tsuchida, Shinji; Fujikura, Katsunori

2014-01-01

Deep-sea alvinellid worm species endemic to hydrothermal vents, such as Alvinella and Paralvinella, are considered to be among the most thermotolerant animals known with their adaptability to toxic heavy metals, and tolerance of highly reductive and oxidative stressful environments. Despite the number of recent studies focused on their overall transcriptomic, proteomic, and metabolic stabilities, little is known regarding their sensory receptor cells and electrically active neuro-processing centers, and how these can tolerate and function in such harsh conditions. We examined the extra- and intracellular organizations of the epidermal ciliated sensory cells and their higher centers in the central nervous system through immunocytochemical, ultrastructural, and neurotracing analyses. We observed that these cells were rich in mitochondria and possessed many electron-dense granules, and identified specialized glial cells and serial myelin-like repeats in the head sensory systems of Paralvinella hessleri. Additionally, we identified the major epidermal sensory pathways, in which a pair of distinct mushroom bodies-like or small interneuron clusters was observed. These sensory learning and memory systems are commonly found in insects and annelids, but the alvinellid inputs are unlikely derived from the sensory ciliary cells of the dorsal head regions. Our evidence provides insight into the cellular and system-wide adaptive structure used to sense, process, and combat the deep-sea hydrothermal vent environment. The alvinellid sensory cells exhibit characteristics of annelid ciliary types, and among the most unique features were the head sensory inputs and structure of the neural cell bodies of the brain, which were surrounded by multiple membranes. We speculated that such enhanced protection is required for the production of normal electrical signals, and to avoid the breakdown of the membrane surrounding metabolically fragile neurons from oxidative stress. Such pivotal acquisition is not broadly found in the all body parts, suggesting the head sensory inputs are specific, and these heterogenetic protection mechanisms may be present in alvinellid worms.

Delayed and lasting effects of deep brain stimulation on locomotion in Parkinson's disease

NASA Astrophysics Data System (ADS)

Beuter, Anne; Modolo, Julien

2009-06-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a variety of motor signs affecting gait, postural stability, and tremor. These symptoms can be improved when electrodes are implanted in deep brain structures and electrical stimulation is delivered chronically at high frequency (>100 Hz). Deep brain stimulation (DBS) onset or cessation affects PD signs with different latencies, and the long-term improvements of symptoms affecting the body axis and those affecting the limbs vary in duration. Interestingly, these effects have not been systematically analyzed and modeled. We compare these timing phenomena in relation to one axial (i.e., locomotion) and one distal (i.e., tremor) signs. We suggest that during DBS, these symptoms are improved by different network mechanisms operating at multiple time scales. Locomotion improvement may involve a delayed plastic reorganization, which takes hours to develop, whereas rest tremor is probably alleviated by an almost instantaneous desynchronization of neural activity in subcortical structures. Even if all PD patients develop both distal and axial symptoms sooner or later, current computational models of locomotion and rest tremor are separate. Furthermore, a few computational models of locomotion focus on PD and none exploring the effect of DBS was found in the literature. We, therefore, discuss a model of a neuronal network during DBS, general enough to explore the subcircuits controlling locomotion and rest tremor simultaneously. This model accounts for synchronization and plasticity, two mechanisms that are believed to underlie the two types of symptoms analyzed. We suggest that a hysteretic effect caused by DBS-induced plasticity and synchronization modulation contributes to the different therapeutic latencies observed. Such a comprehensive, generic computational model of DBS effects, incorporating these timing phenomena, should assist in developing a more efficient, faster, durable treatment of distal and axial signs in PD.

Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation.

PubMed

Quinn, Emma J; Blumenfeld, Zack; Velisar, Anca; Koop, Mandy Miller; Shreve, Lauren A; Trager, Megan H; Hill, Bruce C; Kilbane, Camilla; Henderson, Jaimie M; Brontë-Stewart, Helen

2015-11-01

Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P < 0.003, n = 14), and this was voltage dependent (P < 0.001). Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS. © 2015 International Parkinson and Movement Disorder Society.

Robust modulation of arousal regulation, performance, and frontostriatal activity through central thalamic deep brain stimulation in healthy nonhuman primates

PubMed Central

Ryou, Jae-Wook; Wei, Xuefeng F.; Butson, Christopher R.; Schiff, Nicholas D.; Purpura, Keith P.

2016-01-01

The central thalamus (CT) is a key component of the brain-wide network underlying arousal regulation and sensory-motor integration during wakefulness in the mammalian brain. Dysfunction of the CT, typically a result of severe brain injury (SBI), leads to long-lasting impairments in arousal regulation and subsequent deficits in cognition. Central thalamic deep brain stimulation (CT-DBS) is proposed as a therapy to reestablish and maintain arousal regulation to improve cognition in select SBI patients. However, a mechanistic understanding of CT-DBS and an optimal method of implementing this promising therapy are unknown. Here we demonstrate in two healthy nonhuman primates (NHPs), Macaca mulatta, that location-specific CT-DBS improves performance in visuomotor tasks and is associated with physiological effects consistent with enhancement of endogenous arousal. Specifically, CT-DBS within the lateral wing of the central lateral nucleus and the surrounding medial dorsal thalamic tegmental tract (DTTm) produces a rapid and robust modulation of performance and arousal, as measured by neuronal activity in the frontal cortex and striatum. Notably, the most robust and reliable behavioral and physiological responses resulted when we implemented a novel method of CT-DBS that orients and shapes the electric field within the DTTm using spatially separated DBS leads. Collectively, our results demonstrate that selective activation within the DTTm of the CT robustly regulates endogenous arousal and enhances cognitive performance in the intact NHP; these findings provide insights into the mechanism of CT-DBS and further support the development of CT-DBS as a therapy for reestablishing arousal regulation to support cognition in SBI patients. PMID:27582298

Systematic study of the effects of stimulus parameters and stimulus location on afterdischarges elicited by electrical stimulation in the rat.

PubMed

Shigeto, Hiroshi; Boongird, Atthaporn; Baker, Kenneth; Kellinghaus, Christoph; Najm, Imad; Lüders, Hans

2013-03-01

Electrical brain stimulation is used in a variety of clinical situations, including cortical mapping for epilepsy surgery, cortical stimulation therapy to terminate seizure activity in the cortex, and in deep brain stimulation therapy. However, the effects of stimulus parameters are not fully understood. In this study, we systematically tested the impact of various stimulation parameters on the generation of motor symptoms and afterdischarges (ADs). Focal electrical stimulation was delivered at subdural cortical, intracortical, and hippocampal sites in a rat model. The effects of stimulus parameter on the generation of motor symptoms and on the occurrence of ADs were examined. The effect of stimulus irregularity was tested using random or regular 50Hz stimulation through subdural electrodes. Hippocampal stimulation produced ADs at lower thresholds than neocortical stimulation. Hippocampal stimulation also produced significantly longer ADs. Both in hippocampal and cortical stimulation, when the total current was kept constant with changing pulse width, the threshold for motor symptom or AD was lowest between 50 and 100Hz and higher at both low and high frequencies. However, if the pulse width was fixed, the threshold did not increase above 100Hz and it apparently continued to decrease through 800Hz even if the difference did not reach statistical significance. There was no significant difference between random and regular stimulation. Overall, these results indicate that electrode location and several stimulus parameters including frequency, pulse width, and total electricity are important in electrical stimulation to produce motor symptoms and ADs. Copyright © 2012 Elsevier B.V. All rights reserved.

Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

PubMed

Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

2012-01-01

Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

PubMed Central

Charles, David; Tolleson, Christopher; Davis, Thomas L.; Gill, Chandler E.; Molinari, Anna L.; Bliton, Mark J.; Tramontana, Michael G.; Salomon, Ronald M.; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T.; Neimat, Joseph S.; Konrad, Peter E.

2014-01-01

Background Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. Objective We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. Methods We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Results Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. Conclusions This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease. PMID:23938229

Neuroversion: using electroconvulsive therapy as a bridge to deep brain stimulation implantation.

PubMed

Williams, Nolan R; Sahlem, Greg; Pannu, Jaspreet; Takacs, Istvan; Short, Baron; Revuelta, Gonzalo; George, Mark S

2017-02-01

Parkinson's disease (PD) is a movement disorder with significant neuropsychiatric comorbidities. Electroconvulsive therapy (ECT) is effective in treating these neuropsychiatric symptoms; however, clinicians are reluctant to use ECT in patients with deep brain stimulation (DBS) implantations for fear of damaging the device, as well as potential cognitive side effects. Right unilateral ultra-brief pulse (RUL UBP) ECT has a more favorable cognitive side-effect profile yet has never been reported in PD patients with DBS implants. We present a case series of three patients with a history of PD that all presented with psychiatric decompensation immediately prior to planned DBS surgery. All three patients had DBS electrode(s) in place at the time and an acute course of ECT was utilized in a novel method to "bridge" these individuals to neurosurgery. The patients all experienced symptom resolution (psychosis and/or depression and/or anxiety) without apparent cognitive side effects. This case series not only illustrates that right unilateral ultra-brief pulse can be utilized in patients with DBS electrodes but also illustrates that this intervention can be utilized as a neuromodulatory "bridge", where nonoperative surgical candidates with unstable psychiatric symptoms can be converted to operative candidates in a manner similar to electrical cardioversion.

Effects of deep brain stimulation of the peduncolopontine area on working memory tasks in patients with Parkinson's disease.

PubMed

Costa, Alberto; Carlesimo, Giovanni Augusto; Caltagirone, Carlo; Mazzone, Paolo; Pierantozzi, Mariangela; Stefani, Alessandro; Peppe, Antonella

2010-01-01

The present paper was aimed at investigating the effect of low-frequency electrical stimulation (25 Hz) of the peduncolopontine (PPN) area on working memory (WM) functioning in patients with Parkinson's disease (PD). Five PD patients who underwent simultaneous PPN area- and subthalamic nucleus-deep brain stimulation (DBS) implantation participated in the study. PD patients were evaluated in the morning at least 12 h after antiparkinsonian therapy withdrawal in two conditions: i) after continuous PPN area stimulation (Off Therapy/On PPN: "On" condition); ii) at least 120 min after PPN area had been switched "Off" (Off Ther/Off PPN: "Off" condition). The experimental WM task consisted of an n-back paradigm with verbal and visual-object stimuli. PD patients showed a consistent response time decrease on both the verbal and the visual-object tasks passing from the "Off" to the "On" condition (p < 0.05). However, the accuracy score did not significantly differ between the two experimental conditions. The present findings, although preliminary, suggest that PPN area stimulation facilitates the speed processing of information in the content of WM, possibly through the modulation of the attentional resources.

History of functional neurosurgery.

PubMed

Iskandar, B J; Nashold, B S

1995-01-01

Whereas in the early days of evil spirits, electric catfish, and phrenology, functional neurosurgery was based on crude observations and dogma, the progress made in neurophysiology at the turn of the century gave the field a strong scientific foundation. Subsequently, the advent of stereotaxis allowed access to deep brain regions and contributed an element of precision. Future directions include the development of frameless stereotaxy; the use of MRI-generated anatomic data, which would circumvent the serious problem of individual variations seen with standard brain atlases; the introduction of various chemicals into brain structures, in an attempt to influence neurochemically mediated disease processes; and finally, the use of the promising techniques of neural transplantation. On hearing of Penfield's intraoperative brain stimulations, Sherrington commented: "It must be great fun to have the physiological preparation speak to you." The idea of therapeutic neurophysiologic interventions is appealing, especially because many disorders show no obvious treatable pathologic cause (e.g., tumor, vascular malformation). As stereotactic technology becomes less cumbersome and more precise, more sophisticated in vivo neurophysiologic preparations become possible. In turn, as our understanding of nervous system physiology grows, our ability to understand pathophysiology and treat disease processes increases.

A novel carbon tipped single micro-optrode for combined optogenetics and electrophysiology

PubMed Central

Vizvári, Attila D.; Bali, Zsolt K.; Márki, Balázs; Nagy, Lili V.; Kónya, Zoltán; Madarász, Dániel; Henn-Mike, Nóra; Varga, Csaba; Hernádi, István

2018-01-01

Optical microelectrodes (optrodes) are used in neuroscience to transmit light into the brain of a genetically modified animal to evoke and record electrical activity from light-sensitive neurons. Our novel micro-optrode solution integrates a light-transmitting 125 micrometer optical fiber and a 9 micrometer carbon monofilament to form an electrical lead element, which is contained in a borosilicate glass sheathing coaxial arrangement ending with a micrometer-sized carbon tip. This novel unit design is stiff and slender enough to be used for targeting deep brain areas, and may cause less tissue damage compared with previous models. The center-positioned carbon fiber is less prone to light-induced artifacts than side-lit metal microelectrodes previously presented. The carbon tip is capable of not only recording electrical signals of neuronal origin but can also provide valuable surface area for electron transfer, which is essential in electrochemical (voltammetry, amperometry) or microbiosensor applications. We present details of design and manufacture as well as operational examples of the newly developed single micro-optrode, which includes assessments of 1) carbon tip length–impedance relationship, 2) light transmission capabilities, 3) photoelectric artifacts in carbon fibers, 4) responses to dopamine using fast-scan cyclic voltammetry in vivo, and 5) optogenetic stimulation and spike or local field potential recording from the rat brain transfected with channelrhodopsin-2. With this work, we demonstrate that our novel carbon tipped single micro-optrode may open up new avenues for use in optogenetic stimulation when needing to be combined with extracellular recording, electrochemical, or microbiosensor measurements performed on a millisecond basis. PMID:29513711

The treatment of Parkinson's disease with deep brain stimulation: current issues.

PubMed

Moldovan, Alexia-Sabine; Groiss, Stefan Jun; Elben, Saskia; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars

2015-07-01

Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients' mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.

[Long-term care of Parkinson patients with deep brain stimulation].

PubMed

Allert, N; Barbe, M T; Timmermann, L; Coenen, V A

2011-12-01

For more than 15 years deep brain stimulation of the subthalamic nucleus and globus pallidus internus have become therapeutic options in advanced Parkinson's disease. The number of patients with long-term treatment is increasing steadily. This review focuses on issues of the long-term care of these Parkinson's patients, including differences of the available deep brain stimulation systems, recommendations for follow-up examinations, implications for medical diagnostics and therapies and an algorithm for symptom deterioration. Today, there is no profound evidence that deep brain stimulation prevents disease progression. However, symptomatic relief from motor symptoms is maintained during long-term follow-up and interruption of the therapy remains an exception. © Georg Thieme Verlag KG Stuttgart · New York.

Deep Sequencing to Identify the Causes of Viral Encephalitis

PubMed Central

Chan, Benjamin K.; Wilson, Theodore; Fischer, Kael F.; Kriesel, John D.

2014-01-01

Deep sequencing allows for a rapid, accurate characterization of microbial DNA and RNA sequences in many types of samples. Deep sequencing (also called next generation sequencing or NGS) is being developed to assist with the diagnosis of a wide variety of infectious diseases. In this study, seven frozen brain samples from deceased subjects with recent encephalitis were investigated. RNA from each sample was extracted, randomly reverse transcribed and sequenced. The sequence analysis was performed in a blinded fashion and confirmed with pathogen-specific PCR. This analysis successfully identified measles virus sequences in two brain samples and herpes simplex virus type-1 sequences in three brain samples. No pathogen was identified in the other two brain specimens. These results were concordant with pathogen-specific PCR and partially concordant with prior neuropathological examinations, demonstrating that deep sequencing can accurately identify viral infections in frozen brain tissue. PMID:24699691

Deep brain stimulation effects in dystonia: time course of electrophysiological changes in early treatment.

PubMed

Ruge, Diane; Tisch, Stephen; Hariz, Marwan I; Zrinzo, Ludvic; Bhatia, Kailash P; Quinn, Niall P; Jahanshahi, Marjan; Limousin, Patricia; Rothwell, John C

2011-08-15

Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABA(A) -ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia. Copyright © 2011 Movement Disorder Society.

Long-Term Efficacy of Constant Current Deep Brain Stimulation in Essential Tremor.

PubMed

Rezaei Haddad, Ali; Samuel, Michael; Hulse, Natasha; Lin, Hsin-Ying; Ashkan, Keyoumars

2017-07-01

Ventralis intermedius deep brain stimulation is an established intervention for medication-refractory essential tremor. Newer constant current stimulation technology offers theoretical advantage over the traditional constant voltage systems in terms of delivering a more biologically stable therapy. There are no previous reports on the outcomes of constant current deep brain stimulation in the treatment of essential tremor. This study aimed to evaluate the long-term efficacy of ventralis intermedius constant current deep brain stimulation in patients diagnosed with essential tremor. Essential tremor patients implanted with constant current deep brain stimulation for a minimum of three years were evaluated. Clinical outcomes were assessed using the Fahn-Tolosa-Marin tremor rating scale at baseline and postoperatively at the time of evaluation. The quality of life in the patients was assessed using the Quality of Life in Essential Tremor questionnaire. Ten patients were evaluated with a median age at evaluation of 74 years (range 66-79) and a mean follow up time of 49.7 (range 36-78) months since starting stimulation. Constant current ventralis intermedius deep brain stimulation was well tolerated and effective in all patients with a mean score improvement from 50.7 ± 5.9 to 17.4 ± 5.7 (p = 0.0020) in the total Fahn-Tolosa-Marin rating scale score (65.6%). Furthermore, the total combined mean Quality of Life in Essential Tremor score was improved from 56.2 ± 4.9 to 16.8 ± 3.5 (p value = 0.0059) (70.1%). This report shows that long-term constant current ventralis intermedius deep brain stimulation is a safe and effective intervention for essential tremor patients. © 2017 International Neuromodulation Society.

Subthalamic nucleus deep brain stimulation for Parkinson's disease: evidence for effectiveness and limitations from 12 years' experience.

PubMed

Chan, Anne Y Y; Yeung, Jonas H M; Mok, Vincent C T; Ip, Vincent H L; Wong, Adrian; Kuo, S H; Chan, Danny T M; Zhu, X L; Wong, Edith; Lau, Claire K Y; Wong, Rosanna K M; Tang, Venus; Lau, Christine; Poon, W S

2014-12-01

To present the result and experience of subthalamic nucleus deep brain stimulation for Parkinson's disease. Case series. Prince of Wales Hospital, Hong Kong. A cohort of patients with Parkinson's disease received subthalamic nucleus deep brain stimulation from September 1998 to January 2010. Patient assessment data before and after the operation were collected prospectively. Forty-one patients (21 male and 20 female) with Parkinson's disease underwent bilateral subthalamic nucleus deep brain stimulation and were followed up for a median interval of 12 months. For the whole group, the mean improvements of Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III were 32.5% and 31.5%, respectively (P<0.001). Throughout the years, a multidisciplinary team was gradually built. The deep brain stimulation protocol evolved and was substantiated by updated patient selection criteria and outcome assessment, integrated imaging and neurophysiological targeting, refinement of surgical technique as well as the accumulation of experience in deep brain stimulation programming. Most of the structural improvement occurred before mid-2005. Patients receiving the operation before June 2005 (19 cases) and after (22 cases) were compared; the improvements in UPDRS part III were 13.2% and 55.2%, respectively (P<0.001). There were three operative complications (one lead migration, one cerebral haematoma, and one infection) in the group operated on before 2005. There was no operative mortality. The functional state of Parkinson's disease patients with motor disabilities refractory to best medical treatment improved significantly after subthalamic nucleus deep brain stimulation. A dedicated multidisciplinary team building, refined protocol for patient selection and assessment, improvement of targeting methods, meticulous surgical technique, and experience in programming are the key factors contributing to the improved outcome.

Transmission in near-infrared optical windows for deep brain imaging.

PubMed

Shi, Lingyan; Sordillo, Laura A; Rodríguez-Contreras, Adrián; Alfano, Robert

2016-01-01

Near-infrared (NIR) radiation has been employed using one- and two-photon excitation of fluorescence imaging at wavelengths 650-950 nm (optical window I) for deep brain imaging; however, longer wavelengths in NIR have been overlooked due to a lack of suitable NIR-low band gap semiconductor imaging detectors and/or femtosecond laser sources. This research introduces three new optical windows in NIR and demonstrates their potential for deep brain tissue imaging. The transmittances are measured in rat brain tissue in the second (II, 1,100-1,350 nm), third (III, 1,600-1,870 nm), and fourth (IV, centered at 2,200 nm) NIR optical tissue windows. The relationship between transmission and tissue thickness is measured and compared with the theory. Due to a reduction in scattering and minimal absorption, window III is shown to be the best for deep brain imaging, and windows II and IV show similar but better potential for deep imaging than window I. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Essential Tremor

MedlinePlus

... individuals. Deep brain stimulation uses a surgically implanted, battery-operated medical device called a neurostimulator to delivery ... individuals. Deep brain stimulation uses a surgically implanted, battery-operated medical device called a neurostimulator to delivery ...

[Obsessive-compulsive disorder, a new model of basal ganglia dysfunction? Elements from deep brain stimulation studies].

PubMed

Haynes, W I A; Millet, B; Mallet, L

2012-01-01

Deep brain stimulation was first developed for movement disorders but is now being offered as a therapeutic alternative in severe psychiatric disorders after the failure of conventional therapies. One of such pathologies is obsessive-compulsive disorder. This disorder which associates intrusive thoughts (obsessions) and repetitive irrepressible rituals (compulsions) is characterized by a dysfunction of a cortico-subcortical loop. After having reviewed the pathophysiological evidence to show why deep brain stimulation was an interesting path to take for severe and resistant cases of obsessive-compulsive disorder, we will present the results of the different clinical trials. Finally, we will provide possible mechanisms for the effects of deep brain stimulation in this pathology. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

The treatment of Parkinson's disease with deep brain stimulation: current issues

PubMed Central

Moldovan, Alexia-Sabine; Groiss, Stefan Jun; Elben, Saskia; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars

2015-01-01

Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients’ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation. PMID:26330809

Dynamic risk control by human nucleus accumbens

PubMed Central

Lopez-Sosa, Fernando; Gonzalez-Rosa, Javier Jesus; Galarza, Ana; Avecillas, Josue; Pineda-Pardo, Jose Angel; Lopez-Ibor, Juan José; Reneses, Blanca; Barcia, Juan Antonio

2015-01-01

Real-world decisions about reward often involve a complex counterbalance of risk and value. Although the nucleus accumbens has been implicated in the underlying neural substrate, its criticality to human behaviour remains an open question, best addressed with interventional methodology that probes the behavioural consequences of focal neural modulation. Combining a psychometric index of risky decision-making with transient electrical modulation of the nucleus accumbens, here we reveal profound, highly dynamic alteration of the relation between probability of reward and choice during therapeutic deep brain stimulation in four patients with treatment-resistant psychiatric disease. Short-lived phasic electrical stimulation of the region of the nucleus accumbens dynamically altered risk behaviour, transiently shifting the psychometric function towards more risky decisions only for the duration of stimulation. A critical, on-line role of human nucleus accumbens in dynamic risk control is thereby established. PMID:26428667

Brain organization and specialization in deep-sea chondrichthyans.

PubMed

Yopak, Kara E; Montgomery, John C

2008-01-01

Chondrichthyans occupy a basal place in vertebrate evolution and offer a relatively unexplored opportunity to study the evolution of vertebrate brains. This study examines the brain morphology of 22 species of deep-sea sharks and holocephalans, in relation to both phylogeny and ecology. Both relative brain size (expressed as residuals) and the relative development of the five major brain areas (telencephalon, diencephalon, mesencephalon, cerebellum, and medulla) were assessed. The cerebellar-like structures, which receive projections from the electroreceptive and lateral line organs, were also examined as a discrete part of the medulla. Although the species examined spanned three major chondrichthyan groupings (Squalomorphii, Galeomorphii, Holocephali), brain size and the relative development of the major brain areas did not track phylogenetic groupings. Rather, a hierarchical cluster analysis performed on the deep-sea sharks and holocephalans shows that these species all share the common characteristics of a relatively reduced telencephalon and smooth cerebellar corpus, as well as extreme relative enlargement of the medulla, specifically the cerebellar-like lobes. Although this study was not a functional analysis, it provides evidence that brain variation in deep-sea chondichthyans shows adaptive patterns in addition to underlying phylogenetic patterns, and that particular brain patterns might be interpreted as 'cerebrotypes'. (c) 2008 S. Karger AG, Basel

Constructing fine-granularity functional brain network atlases via deep convolutional autoencoder.

PubMed

Zhao, Yu; Dong, Qinglin; Chen, Hanbo; Iraji, Armin; Li, Yujie; Makkie, Milad; Kou, Zhifeng; Liu, Tianming

2017-12-01

State-of-the-art functional brain network reconstruction methods such as independent component analysis (ICA) or sparse coding of whole-brain fMRI data can effectively infer many thousands of volumetric brain network maps from a large number of human brains. However, due to the variability of individual brain networks and the large scale of such networks needed for statistically meaningful group-level analysis, it is still a challenging and open problem to derive group-wise common networks as network atlases. Inspired by the superior spatial pattern description ability of the deep convolutional neural networks (CNNs), a novel deep 3D convolutional autoencoder (CAE) network is designed here to extract spatial brain network features effectively, based on which an Apache Spark enabled computational framework is developed for fast clustering of larger number of network maps into fine-granularity atlases. To evaluate this framework, 10 resting state networks (RSNs) were manually labeled from the sparsely decomposed networks of Human Connectome Project (HCP) fMRI data and 5275 network training samples were obtained, in total. Then the deep CAE models are trained by these functional networks' spatial maps, and the learned features are used to refine the original 10 RSNs into 17 network atlases that possess fine-granularity functional network patterns. Interestingly, it turned out that some manually mislabeled outliers in training networks can be corrected by the deep CAE derived features. More importantly, fine granularities of networks can be identified and they reveal unique network patterns specific to different brain task states. By further applying this method to a dataset of mild traumatic brain injury study, it shows that the technique can effectively identify abnormal small networks in brain injury patients in comparison with controls. In general, our work presents a promising deep learning and big data analysis solution for modeling functional connectomes, with fine granularities, based on fMRI data. Copyright © 2017 Elsevier B.V. All rights reserved.

Deep convolutional neural network for the automated detection and diagnosis of seizure using EEG signals.

PubMed

Acharya, U Rajendra; Oh, Shu Lih; Hagiwara, Yuki; Tan, Jen Hong; Adeli, Hojjat

2017-09-27

An encephalogram (EEG) is a commonly used ancillary test to aide in the diagnosis of epilepsy. The EEG signal contains information about the electrical activity of the brain. Traditionally, neurologists employ direct visual inspection to identify epileptiform abnormalities. This technique can be time-consuming, limited by technical artifact, provides variable results secondary to reader expertise level, and is limited in identifying abnormalities. Therefore, it is essential to develop a computer-aided diagnosis (CAD) system to automatically distinguish the class of these EEG signals using machine learning techniques. This is the first study to employ the convolutional neural network (CNN) for analysis of EEG signals. In this work, a 13-layer deep convolutional neural network (CNN) algorithm is implemented to detect normal, preictal, and seizure classes. The proposed technique achieved an accuracy, specificity, and sensitivity of 88.67%, 90.00% and 95.00%, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Energy harvesting from arterial blood pressure for powering embedded micro sensors in human brain

NASA Astrophysics Data System (ADS)

Nanda, Aditya; Karami, M. Amin

2017-03-01

This manuscript investigates energy harvesting from arterial blood pressure via the piezoelectric effect for the purpose of powering embedded micro-sensors in the human brain. One of the major hurdles in recording and measuring electrical data in the human nervous system is the lack of implantable and long term interfaces that record neural activity for extended periods of time. Recently, some authors have proposed micro sensors implanted deep in the brain that measure local electrical and physiological data which are then communicated to an external interrogator. This paper proposes a way of powering such interfaces. The geometry of the proposed harvester consists of a piezoelectric, circular, curved bimorph that fits into the blood vessel (specifically, the Carotid artery) and undergoes bending motion because of blood pressure variation. In addition, the harvester thickness is constrained such that it does not modify arterial wall dynamics. This transforms the problem into a known strain problem and the integral form of Gauss's law is used to obtain an equation relating arterial wall motion to the induced voltage. The theoretical model is validated by means of a Multiphysics 3D-FEA simulation comparing the harvested power at different load resistances. The peak harvested power achieved for the Carotid artery (proximal to Brain), with PZT-5H, was 11.7 μW. The peak power for the Aorta was 203.4 μW. Further, the variation of harvested power with variation in the harvester width and thickness, arterial contractility, and pulse rate is investigated. Moreover, potential application of the harvester as a chronic, implantable and real-time Blood pressure sensor is considered. Energy harvested via this mechanism will also have applications in long-term, implantable Brain Micro-stimulation.

A comparative study of approaches to compute the field distribution of deep brain stimulation in the Hemiparkinson rat model.

PubMed

Bohme, Andrea; van Rienen, Ursula

2016-08-01

Computational modeling of the stimulating field distribution during Deep Brain Stimulation provides an opportunity to advance our knowledge of this neurosurgical therapy for Parkinson's disease. There exist several approaches to model the target region for Deep Brain Stimulation in Hemi-parkinson Rats with volume conductor models. We have described and compared the normalized mapping approach as well as the modeling with three-dimensional structures, which include curvilinear coordinates to assure an anatomically realistic conductivity tensor orientation.

Development of the Mayo Investigational Neuromodulation Control System: toward a closed-loop electrochemical feedback system for deep brain stimulation

PubMed Central

Chang, Su-Youne; Kimble, Christopher J.; Kim, Inyong; Paek, Seungleal B.; Kressin, Kenneth R.; Boesche, Joshua B.; Whitlock, Sidney V.; Eaker, Diane R.; Kasasbeh, Aimen; Horne, April E.; Blaha, Charles D.; Bennet, Kevin E.; Lee, Kendall H.

2014-01-01

Object Conventional deep brain stimulation (DBS) devices continue to rely on an open-loop system in which stimulation is independent of functional neural feedback. The authors previously proposed that as the foundation of a DBS “smart” device, a closed-loop system based on neurochemical feedback, may have the potential to improve therapeutic outcomes. Alterations in neurochemical release are thought to be linked to the clinical benefit of DBS, and fast-scan cyclic voltammetry (FSCV) has been shown to be effective for recording these evoked neurochemical changes. However, the combination of FSCV with conventional DBS devices interferes with the recording and identification of the evoked analytes. To integrate neurochemical recording with neurostimulation, the authors developed the Mayo Investigational Neuromodulation Control System (MINCS), a novel, wirelessly controlled stimulation device designed to interface with FSCV performed by their previously described Wireless Instantaneous Neurochemical Concentration Sensing System (WINCS). Methods To test the functionality of these integrated devices, various frequencies of electrical stimulation were applied by MINCS to the medial forebrain bundle of the anesthetized rat, and striatal dopamine release was recorded by WINCS. The parameters for FSCV in the present study consisted of a pyramidal voltage waveform applied to the carbon-fiber microelectrode every 100 msec, ramping between −0.4 V and +1.5 V with respect to an Ag/AgCl reference electrode at a scan rate of either 400 V/sec or 1000 V/sec. The carbon-fiber microelectrode was held at the baseline potential of −0.4 V between scans. Results By using MINCS in conjunction with WINCS coordinated through an optic fiber, the authors interleaved intervals of electrical stimulation with FSCV scans and thus obtained artifact-free wireless FSCV recordings. Electrical stimulation of the medial forebrain bundle in the anesthetized rat by MINCS elicited striatal dopamine release that was time-locked to stimulation and increased progressively with stimulation frequency. Conclusions Here, the authors report a series of proof-of-principle tests in the rat brain demonstrating MINCS to be a reliable and flexible stimulation device that, when used in conjunction with WINCS, performs wirelessly controlled stimulation concurrent with artifact-free neurochemical recording. These findings suggest that the integration of neurochemical recording with neurostimulation may be a useful first step toward the development of a closed-loop DBS system for human application. PMID:24116724

75 FR 51467 - ASK (Assess Specific Kinds of CHILDREN Challenges for Neurologic Devices) Study Children Workshop...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-20

..., including cochlear implants, deep brain stimulators, hydrocephalus shunts, spinal cord stimulators, and... pediatric populations, including cochlear implants, deep brain stimulators, hydrocephalus shunts, spinal...

Deep brain stimulation surgery for alcohol addiction.

PubMed

Voges, Juergen; Müller, Ulf; Bogerts, Bernhard; Münte, Thomas; Heinze, Hans-Jochen

2013-01-01

The consequences of chronic alcohol dependence cause important health and economic burdens worldwide. Relapse rates after standard treatment (medication and psychotherapy) are high. There is evidence from in vivo investigations and from studies in patients that the brain's reward system is critically involved in the development and maintenance of addictive behavior, suggesting that modification of this system could significantly improve the prognosis of addictive patients. Motivated by an accidental observation, we used the nucleus accumbens (NAc), which has a central position in the dopaminergic reward system for deep brain stimulation (DBS) of alcohol addiction. We report our first experiences with NAc DBS for alcohol dependence and review the literature addressing the mechanisms leading to addiction. Five patients were treated off-label with bilateral NAc DBS for severe alcohol addiction (average follow-up 38 months). All patients experienced significant and ongoing improvement of craving. Two patients remained completely abstinent for more than 4 years. NAc stimulation was tolerated without permanent side effects. Simultaneous recording of local field potentials from the target area and surface electroencephalography while patients performed neuropsychological tasks gave a hint on the pivotal role of the NAc in processing alcohol-related cues. To our knowledge, the data presented here reflect the first attempt to treat alcohol-addicted patients with NAc DBS. Electrical NAc stimulation probably counterbalances the effect of drug-related stimuli triggering involuntarily drug-seeking behavior. Meanwhile, two prospective clinical studies using randomized, double-blind, and crossover stimulation protocols for DBS are underway to corroborate these preliminary results. Published by Elsevier Inc.

Mechanisms and targets of deep brain stimulation in movement disorders.

PubMed

Johnson, Matthew D; Miocinovic, Svjetlana; McIntyre, Cameron C; Vitek, Jerrold L

2008-04-01

Chronic electrical stimulation of the brain, known as deep brain stimulation (DBS), has become a preferred surgical treatment for medication-refractory movement disorders. Despite its remarkable clinical success, the therapeutic mechanisms of DBS are still not completely understood, limiting opportunities to improve treatment efficacy and simplify selection of stimulation parameters. This review addresses three questions essential to understanding the mechanisms of DBS. 1) How does DBS affect neuronal tissue in the vicinity of the active electrode or electrodes? 2) How do these changes translate into therapeutic benefit on motor symptoms? 3) How do these effects depend on the particular site of stimulation? Early hypotheses proposed that stimulation inhibited neuronal activity at the site of stimulation, mimicking the outcome of ablative surgeries. Recent studies have challenged that view, suggesting that although somatic activity near the DBS electrode may exhibit substantial inhibition or complex modulation patterns, the output from the stimulated nucleus follows the DBS pulse train by direct axonal excitation. The intrinsic activity is thus replaced by high-frequency activity that is time-locked to the stimulus and more regular in pattern. These changes in firing pattern are thought to prevent transmission of pathologic bursting and oscillatory activity, resulting in the reduction of disease symptoms through compensatory processing of sensorimotor information. Although promising, this theory does not entirely explain why DBS improves motor symptoms at different latencies. Understanding these processes on a physiological level will be critically important if we are to reach the full potential of this powerful tool.

A computational model to compare different investment scenarios for mini-stereotactic frame approach to deep brain stimulation surgery.

PubMed

Lanotte, M; Cavallo, M; Franzini, A; Grifi, M; Marchese, E; Pantaleoni, M; Piacentino, M; Servello, D

2010-09-01

Deep brain stimulation (DBS) alleviates symptoms of many neurological disorders by applying electrical impulses to the brain by means of implanted electrodes, generally put in place using a conventional stereotactic frame. A new image guided disposable mini-stereotactic system has been designed to help shorten and simplify DBS procedures when compared to standard stereotaxy. A small number of studies have been conducted which demonstrate localization accuracies of the system similar to those achievable by the conventional frame. However no data are available to date on the economic impact of this new frame. The aim of this paper was to develop a computational model to evaluate the investment required to introduce the image guided mini-stereotactic technology for stereotactic DBS neurosurgery. A standard DBS patient care pathway was developed and related costs were analyzed. A differential analysis was conducted to capture the impact of introducing the image guided system on the procedure workflow. The analysis was carried out in five Italian neurosurgical centers. A computational model was developed to estimate upfront investments and surgery costs leading to a definition of the best financial option to introduce the new frame. Investments may vary from Euro 1.900 (purchasing of Image Guided [IG] mini-stereotactic frame only) to Euro 158.000.000. Moreover the model demonstrates how the introduction of the IG mini-stereotactic frame doesn't substantially affect the DBS procedure costs.

Magnetothermal genetic deep brain stimulation of motor behaviors in awake, freely moving mice

PubMed Central

Zhang, Qian; Castellanos Rubio, Idoia; del Pino, Pablo

2017-01-01

Establishing how neurocircuit activation causes particular behaviors requires modulating the activity of specific neurons. Here, we demonstrate that magnetothermal genetic stimulation provides tetherless deep brain activation sufficient to evoke motor behavior in awake mice. The approach uses alternating magnetic fields to heat superparamagnetic nanoparticles on the neuronal membrane. Neurons, heat-sensitized by expressing TRPV1 are activated with magnetic field application. Magnetothermal genetic stimulation in the motor cortex evoked ambulation, deep brain stimulation in the striatum caused rotation around the body-axis, and stimulation near the ridge between ventral and dorsal striatum caused freezing-of-gait. The duration of the behavior correlated tightly with field application. This approach provides genetically and spatially targetable, repeatable and temporarily precise activation of deep-brain circuits without the need for surgical implantation of any device. PMID:28826470

[Emotion and basal ganglia (II): what can we learn from subthalamic nucleus deep brain stimulation in Parkinson's disease?].

PubMed

Péron, J; Dondaine, T

2012-01-01

The subthalamic nucleus deep-brain stimulation Parkinson's disease patient model seems to represent a unique opportunity for studying the functional role of the basal ganglia and notably the subthalamic nucleus in human emotional processing. Indeed, in addition to constituting a therapeutic advance for severely disabled Parkinson's disease patients, deep brain stimulation is a technique, which selectively modulates the activity of focal structures targeted by surgery. There is growing evidence of a link between emotional impairments and deep-brain stimulation of the subthalamic nucleus. In this context, according to the definition of emotional processing exposed in the companion paper available in this issue, the aim of the present review will consist in providing a synopsis of the studies that investigated the emotional disturbances observed in subthalamic nucleus deep brain stimulation Parkinson's disease patients. This review leads to the conclusion that several emotional components would be disrupted after subthalamic nucleus deep brain stimulation in Parkinson's disease: subjective feeling, neurophysiological activation, and motor expression. Finally, after a description of the limitations of this study model, we discuss the functional role of the subthalamic nucleus (and the striato-thalamo-cortical circuits in which it is involved) in emotional processing. It seems reasonable to conclude that the striato-thalamo-cortical circuits are indeed involved in emotional processing and that the subthalamic nucleus plays a central in role the human emotional architecture. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Mood stability in Parkinson disease following deep brain stimulation: a 6-month prospective follow-up study.

PubMed

Chopra, Amit; Abulseoud, Osama A; Sampson, Shirlene; Lee, Kendall H; Klassen, Bryan T; Fields, Julie A; Matsumoto, Joseph Y; Adams, Andrea C; Stoppel, Cynthia J; Geske, Jennifer R; Frye, Mark A

2014-01-01

Deep brain stimulation for Parkinson disease has been associated with psychiatric adverse effects including anxiety, depression, mania, psychosis, and suicide. The purpose of this study was to evaluate the safety of deep brain stimulation in a large Parkinson disease clinical practice. Patients approved for surgery by the Mayo Clinic deep brain stimulation clinical committee participated in a 6-month prospective naturalistic follow-up study. In addition to the Unified Parkinson's Disease Rating Scale, stability and psychiatric safety were measured using the Beck Depression Inventory, Hamilton Depression Rating Scale, and Young Mania Rating scale. Outcomes were compared in patients with Parkinson disease who had a psychiatric history to those with no co-morbid psychiatric history. The study was completed by 49 of 54 patients. Statistically significant 6-month baseline to end-point improvement was found in motor and mood scales. No significant differences were found in psychiatric outcomes based on the presence or absence of psychiatric comorbidity. Our study suggests that patients with Parkinson disease who have a history of psychiatric co-morbidity can safely respond to deep brain stimulation with no greater risk of psychiatric adverse effect occurrence. A multidisciplinary team approach, including careful psychiatric screening ensuring mood stabilization and psychiatric follow-up, should be viewed as standard of care to optimize the psychiatric outcome in the course of deep brain stimulation treatment. © 2013 Published by The Academy of Psychosomatic Medicine on behalf of The Academy of Psychosomatic Medicine.

Recording evoked potentials during deep brain stimulation: development and validation of instrumentation to suppress the stimulus artefact

PubMed Central

Kent, A R; Grill, W M

2012-01-01

Deep brain stimulation (DBS) is an effective treatment for movement disorders, but the selection of stimulus parameters is a clinical burden and often yields sub-optimal outcomes for patients. Measurement of electrically evoked compound action potentials (ECAPs) during DBS could offer insight into the type and spatial extent of neural element activation and provide a potential feedback signal for the rational selection of stimulus parameters and closed-loop DBS. However, recording ECAPs presents a significant technical challenge due to the large stimulus artefact, which can saturate recording amplifiers and distort short latency ECAP signals. We developed DBS-ECAP recording instrumentation combining commercial amplifiers and circuit elements in a serial configuration to reduce the stimulus artefact and enable high fidelity recording. We used an electrical circuit equivalent model of the instrumentation to understand better the sources of the stimulus artefact and the mechanisms of artefact reduction by the circuit elements. In vitro testing validated the capability of the instrumentation to suppress the stimulus artefact and increase gain by a factor of 1,000 to 5,000 compared to a conventional biopotential amplifier. The distortion of mock ECAP (mECAP) signals was measured across stimulation parameters, and the instrumentation enabled high fidelity recording of mECAPs with latencies of only 0.5 ms for DBS pulse widths of 50 to 100 μs/phase. Subsequently, the instrumentation was used to record in vivo ECAPs, without contamination by the stimulus artefact, during thalamic DBS in an anesthetized cat. The characteristics of the physiological ECAP were dependent on stimulation parameters. The novel instrumentation enables high fidelity ECAP recording and advances the potential use of the ECAP as a feedback signal for the tuning of DBS parameters. PMID:22510375

Laser treatments of deep-seated brain lesions

NASA Astrophysics Data System (ADS)

Ward, Helen A.

1997-06-01

The five year survival rate of deep-seated malignant brain tumors after surgery/radiotherapy is virtually 100 percent mortality. Special problems include: (1) Lesions often present late. (2) Position: lesion overlies vital structures, so complete surgical/radiotherapy lesion destruction can damage vital brain-stem functions. (3) Difficulty in differentiating normal brain form malignant lesions. This study aimed to use the unique properties of the laser: (a) to minimize damage during surgical removal of deep-seated brain lesions by operating via fine optic fibers; and (b) to employ the propensity of certain lasers for absorption of dyes and absorption and induction of fluorescence in some brain substances, to differentiate borders of malignant and normal brain, for more complete tumor removal. In the method a fine laser endoscopic technique was devised for removal of brain lesions. The results of this technique, were found to minimize and accurately predict the extent of thermal damage and shock waves to within 1-2mm of the surgical laser beam. Thereby it eliminated the 'popcorn' effect.

TuMore: generation of synthetic brain tumor MRI data for deep learning based segmentation approaches

NASA Astrophysics Data System (ADS)

Lindner, Lydia; Pfarrkirchner, Birgit; Gsaxner, Christina; Schmalstieg, Dieter; Egger, Jan

2018-03-01

Accurate segmentation and measurement of brain tumors plays an important role in clinical practice and research, as it is critical for treatment planning and monitoring of tumor growth. However, brain tumor segmentation is one of the most challenging tasks in medical image analysis. Since manual segmentations are subjective, time consuming and neither accurate nor reliable, there exists a need for objective, robust and fast automated segmentation methods that provide competitive performance. Therefore, deep learning based approaches are gaining interest in the field of medical image segmentation. When the training data set is large enough, deep learning approaches can be extremely effective, but in domains like medicine, only limited data is available in the majority of cases. Due to this reason, we propose a method that allows to create a large dataset of brain MRI (Magnetic Resonance Imaging) images containing synthetic brain tumors - glioblastomas more specifically - and the corresponding ground truth, that can be subsequently used to train deep neural networks.

Parkinsonian gait improves with bilateral subthalamic nucleus deep brain stimulation during cognitive multi-tasking.

PubMed

Chenji, Gaurav; Wright, Melissa L; Chou, Kelvin L; Seidler, Rachael D; Patil, Parag G

2017-05-01

Gait impairment in Parkinson's disease reduces mobility and increases fall risk, particularly during cognitive multi-tasking. Studies suggest that bilateral subthalamic deep brain stimulation, a common surgical therapy, degrades motor performance under cognitive dual-task conditions, compared to unilateral stimulation. To measure the impact of bilateral versus unilateral subthalamic deep brain stimulation on walking kinematics with and without cognitive dual-tasking. Gait kinematics of seventeen patients with advanced Parkinson's disease who had undergone bilateral subthalamic deep brain stimulation were examined off medication under three stimulation states (bilateral, unilateral left, unilateral right) with and without a cognitive challenge, using an instrumented walkway system. Consistent with earlier studies, gait performance declined for all six measured parameters under cognitive dual-task conditions, independent of stimulation state. However, bilateral stimulation produced greater improvements in step length and double-limb support time than unilateral stimulation, and achieved similar performance for other gait parameters. Contrary to expectations from earlier studies of dual-task motor performance, bilateral subthalamic deep brain stimulation may assist in maintaining temporal and spatial gait performance under cognitive dual-task conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

And Then There Was Light: Perspectives of Optogenetics for Deep Brain Stimulation and Neuromodulation

PubMed Central

Delbeke, Jean; Hoffman, Luis; Mols, Katrien; Braeken, Dries; Prodanov, Dimiter

2017-01-01

Deep Brain Stimulation (DBS) has evolved into a well-accepted add-on treatment for patients with severe Parkinsons disease as well as for other chronic neurological conditions. The focal action of electrical stimulation can yield better responses and it exposes the patient to fewer side effects compared to pharmaceuticals distributed throughout the body toward the brain. On the other hand, the current practice of DBS is hampered by the relatively coarse level of neuromodulation achieved. Optogenetics, in contrast, offers the perspective of much more selective actions on the various physiological structures, provided that the stimulated cells are rendered sensitive to the action of light. Optogenetics has experienced tremendous progress since its first in vivo applications about 10 years ago. Recent advancements of viral vector technology for gene transfer substantially reduce vector-associated cytotoxicity and immune responses. This brings about the possibility to transfer this technology into the clinic as a possible alternative to DBS and neuromodulation. New paths could be opened toward a rich panel of clinical applications. Some technical issues still limit the long term use in humans but realistic perspectives quickly emerge. Despite a rapid accumulation of observations about patho-physiological mechanisms, it is still mostly serendipity and empiric adjustments that dictate clinical practice while more efficient logically designed interventions remain rather exceptional. Interestingly, it is also very much the neuro technology developed around optogenetics that offers the most promising tools to fill in the existing knowledge gaps about brain function in health and disease. The present review examines Parkinson's disease and refractory epilepsy as use cases for possible optogenetic stimulation therapies. PMID:29311765

Automatic recognition of holistic functional brain networks using iteratively optimized convolutional neural networks (IO-CNN) with weak label initialization.

PubMed

Zhao, Yu; Ge, Fangfei; Liu, Tianming

2018-07-01

fMRI data decomposition techniques have advanced significantly from shallow models such as Independent Component Analysis (ICA) and Sparse Coding and Dictionary Learning (SCDL) to deep learning models such Deep Belief Networks (DBN) and Convolutional Autoencoder (DCAE). However, interpretations of those decomposed networks are still open questions due to the lack of functional brain atlases, no correspondence across decomposed or reconstructed networks across different subjects, and significant individual variabilities. Recent studies showed that deep learning, especially deep convolutional neural networks (CNN), has extraordinary ability of accommodating spatial object patterns, e.g., our recent works using 3D CNN for fMRI-derived network classifications achieved high accuracy with a remarkable tolerance for mistakenly labelled training brain networks. However, the training data preparation is one of the biggest obstacles in these supervised deep learning models for functional brain network map recognitions, since manual labelling requires tedious and time-consuming labours which will sometimes even introduce label mistakes. Especially for mapping functional networks in large scale datasets such as hundreds of thousands of brain networks used in this paper, the manual labelling method will become almost infeasible. In response, in this work, we tackled both the network recognition and training data labelling tasks by proposing a new iteratively optimized deep learning CNN (IO-CNN) framework with an automatic weak label initialization, which enables the functional brain networks recognition task to a fully automatic large-scale classification procedure. Our extensive experiments based on ABIDE-II 1099 brains' fMRI data showed the great promise of our IO-CNN framework. Copyright © 2018 Elsevier B.V. All rights reserved.

Instrumentation to Record Evoked Potentials for Closed-Loop Control of Deep Brain Stimulation

PubMed Central

Kent, Alexander R.; Grill, Warren M.

2012-01-01

Closed-loop deep brain stimulation (DBS) systems offer promise in relieving the clinical burden of stimulus parameter selection and improving treatment outcomes. In such a system, a feedback signal is used to adjust automatically stimulation parameters and optimize the efficacy of stimulation. We explored the feasibility of recording electrically evoked compound action potentials (ECAPs) during DBS for use as a feedback control signal. A novel instrumentation system was developed to suppress the stimulus artifact and amplify the small magnitude, short latency ECAP response during DBS with clinically relevant parameters. In vitro testing demonstrated the capabilities to increase the gain by a factor of 1,000x over a conventional amplifier without saturation, reduce distortion of mock ECAP signals, and make high fidelity recordings of mock ECAPs at latencies of only 0.5 ms following DBS pulses of 50 to 100 μs duration. Subsequently, the instrumentation was used to make in vivo recordings of ECAPs during thalamic DBS in cats, without contamination by the stimulus artifact. The signal characteristics were similar across three experiments, suggesting common neural activation patterns. The ECAP recordings enabled with this novel instrumentation may provide insight into the type and spatial extent of neural elements activated during DBS, and could serve as feedback control signals for closed-loop systems. PMID:22255894

Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson's Disease: a case study.

PubMed

Cunningham, Miles G; Yadollahikhales, Golnaz; Vitaliano, Gordana; van Horne, Craig

2016-11-15

Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression. The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. Five years after initiating DBS, during a routine battery change, an apparent electrical event occurred that triggered the rapid onset of severe depression. Anti-seizure and antidepressant medications were ineffective, and the patient was offered a course of electroconvulsive therapy (ECT), which resulted in complete reversal of her depressive episode. Parkinson's syndrome can be seen after a single closed head injury event. Post-traumatic parkinsonism is responsive to DBS; however, DBS has been associated with an infrequent occurrence of dramatic disruption in mood. ECT is a therapeutic option for patients who develop intractable depressive illness associated with DBS.

Neural targets for relieving parkinsonian rigidity and bradykinesia with pallidal deep brain stimulation

PubMed Central

Zhang, Jianyu; Ghosh, Debabrata; McIntyre, Cameron C.; Vitek, Jerrold L.

2012-01-01

Clinical evidence has suggested that subtle changes in deep brain stimulation (DBS) settings can have differential effects on bradykinesia and rigidity in patients with Parkinson's disease. In this study, we first investigated the degree of improvement in bradykinesia and rigidity during targeted globus pallidus DBS in three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus macaques. Behavioral outcomes of DBS were then coupled with detailed, subject-specific computational models of neurons in the globus pallidus internus (GPi), globus pallidus externus (GPe), and internal capsule (IC) to determine which neuronal pathways when modulated with high-frequency electrical stimulation best correlate with improvement in motor symptoms. The modeling results support the hypothesis that multiple neuronal pathways can underlie the therapeutic effect of DBS on parkinsonian bradykinesia and rigidity. Across all three subjects, improvements in rigidity correlated most strongly with spread of neuronal activation into IC, driving a small percentage of fibers within this tract (<10% on average). The most robust effect on bradykinesia resulted from stimulating a combination of sensorimotor axonal projections within the GP, specifically at the site of the medial medullary lamina. Thus the beneficial effects of pallidal DBS for parkinsonian symptoms may occur from multiple targets within and near the target nucleus. PMID:22514292

Evaluation of Phonatory Behavior and Voice Quality in Patients with Multiple Sclerosis Treated with Deep Brain Stimulation.

PubMed

Pützer, Manfred; Wokurek, Wolfgang; Moringlane, Jean Richard

2017-07-01

The effect of deep brain stimulation (DBS) on phonatory behavior and voice quality in eight patients with multiple sclerosis (MS) was examined instrumentally and perceptually. The acoustic signals of vowel productions obtained from patients (produced with and without stimulation) and from a group of 16 healthy control speakers were analyzed to prove statistically the changes of phonatory behavior and voice quality. This is a randomized study. Firstly, a new parametrization was used to determine phonatory behavior. Secondly, a perceptual evaluation of voice quality of the same speech material was performed. With stimulation, phonation has a greater tendency to be strained. The results of perceptual evaluation support this strained phonation behavior under stimulation, resulting in a smaller degree of breathiness ratings of all raters. Without stimulation, an impaired and partly disturbed adduction of the vocal folds can be shown. These findings are also supported in the perceptual experiment providing a higher degree of hoarseness ratings of all raters for these signals. High-frequency electrical impulses to the thalamus in patients with MS influence the phonatory behavior of their vocal folds. The results suggest the need for long-term monitoring of phonatory behavior during DBS to initiate adequate treatments without delay. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Thoracic surgery in patients with an implanted neurostimulator device.

PubMed

Meyring, Kristina; Zehnder, Adrian; Schmid, Ralph A; Kocher, Gregor J

2017-10-01

Movement disorders such as Parkinson's disease are increasingly treated with deep brain stimulators. Being implanted in a subcutaneous pocket in the chest region, thoracic surgical procedures can interfere with such devices, as they are sensible to external electromagnetic forces. Monopolar electrocautery can lead to dysfunction of the device or damage of the brain tissue caused by heat. We report a series of 3 patients with deep brain stimulators who underwent thoracic surgery. By turning off the deep brain stimulators before surgery and avoiding the use of monopolar cautery, electromagnetic interactions were avoided in all patients. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

The use of neurocomputational models as alternatives to animal models in the development of electrical brain stimulation treatments.

PubMed

Beuter, Anne

2017-05-01

Recent publications call for more animal models to be used and more experiments to be performed, in order to better understand the mechanisms of neurodegenerative disorders, to improve human health, and to develop new brain stimulation treatments. In response to these calls, some limitations of the current animal models are examined by using Deep Brain Stimulation (DBS) in Parkinson's disease as an illustrative example. Without focusing on the arguments for or against animal experimentation, or on the history of DBS, the present paper argues that given recent technological and theoretical advances, the time has come to consider bioinspired computational modelling as a valid alternative to animal models, in order to design the next generation of human brain stimulation treatments. However, before computational neuroscience is fully integrated in the translational process and used as a substitute for animal models, several obstacles need to be overcome. These obstacles are examined in the context of institutional, financial, technological and behavioural lock-in. Recommendations include encouraging agreement to change long-term habitual practices, explaining what alternative models can achieve, considering economic stakes, simplifying administrative and regulatory constraints, and carefully examining possible conflicts of interest. 2017 FRAME.

Red and NIR light dosimetry in the human deep brain

NASA Astrophysics Data System (ADS)

Pitzschke, A.; Lovisa, B.; Seydoux, O.; Zellweger, M.; Pfleiderer, M.; Tardy, Y.; Wagnières, G.

2015-04-01

Photobiomodulation (PBM) appears promising to treat the hallmarks of Parkinson’s Disease (PD) in cellular or animal models. We measured light propagation in different areas of PD-relevant deep brain tissue during transcranial, transsphenoidal illumination (at 671 and 808 nm) of a cadaver head and modeled optical parameters of human brain tissue using Monte-Carlo simulations. Gray matter, white matter, cerebrospinal fluid, ventricles, thalamus, pons, cerebellum and skull bone were processed into a mesh of the skull (158 × 201 × 211 voxels; voxel side length: 1 mm). Optical parameters were optimized from simulated and measured fluence rate distributions. The estimated μeff for the different tissues was in all cases larger at 671 than at 808 nm, making latter a better choice for light delivery in the deep brain. Absolute values were comparable to those found in the literature or slightly smaller. The effective attenuation in the ventricles was considerably larger than literature values. Optimization yields a new set of optical parameters better reproducing the experimental data. A combination of PBM via the sphenoid sinus and oral cavity could be beneficial. A 20-fold higher efficiency of light delivery to the deep brain was achieved with ventricular instead of transcranial illumination. Our study demonstrates that it is possible to illuminate deep brain tissues transcranially, transsphenoidally and via different application routes. This opens therapeutic options for sufferers of PD or other cerebral diseases necessitating light therapy.

Theta-burst microstimulation in the human entorhinal area improves memory specificity.

PubMed

Titiz, Ali S; Hill, Michael R H; Mankin, Emily A; M Aghajan, Zahra; Eliashiv, Dawn; Tchemodanov, Natalia; Maoz, Uri; Stern, John; Tran, Michelle E; Schuette, Peter; Behnke, Eric; Suthana, Nanthia A; Fried, Itzhak

2017-10-24

The hippocampus is critical for episodic memory, and synaptic changes induced by long-term potentiation (LTP) are thought to underlie memory formation. In rodents, hippocampal LTP may be induced through electrical stimulation of the perforant path. To test whether similar techniques could improve episodic memory in humans, we implemented a microstimulation technique that allowed delivery of low-current electrical stimulation via 100 μm -diameter microelectrodes. As thirteen neurosurgical patients performed a person recognition task, microstimulation was applied in a theta-burst pattern, shown to optimally induce LTP. Microstimulation in the right entorhinal area during learning significantly improved subsequent memory specificity for novel portraits; participants were able both to recognize previously-viewed photos and reject similar lures. These results suggest that microstimulation with physiologic level currents-a radical departure from commonly used deep brain stimulation protocols-is sufficient to modulate human behavior and provides an avenue for refined interrogation of the circuits involved in human memory.

Evaluation method for in situ electric field in standardized human brain for different transcranial magnetic stimulation coils

NASA Astrophysics Data System (ADS)

Iwahashi, Masahiro; Gomez-Tames, Jose; Laakso, Ilkka; Hirata, Akimasa

2017-03-01

This study proposes a method to evaluate the electric field induced in the brain by transcranial magnetic stimulation (TMS) to realize focal stimulation in the target area considering the inter-subject difference of the brain anatomy. The TMS is a non-invasive technique used for treatment/diagnosis, and it works by inducing an electric field in a specific area of the brain via a coil-induced magnetic field. Recent studies that report on the electric field distribution in the brain induced by TMS coils have been limited to simplified human brain models or a small number of detailed human brain models. Until now, no method has been developed that appropriately evaluates the coil performance for a group of subjects. In this study, we first compare the magnetic field and the magnetic vector potential distributions to determine if they can be used as predictors of the TMS focality derived from the electric field distribution. Next, the hotspots of the electric field on the brain surface of ten subjects using six coils are compared. Further, decisive physical factors affecting the focality of the induced electric field by different coils are discussed by registering the computed electric field in a standard brain space for the first time, so as to evaluate coil characteristics for a large population of subjects. The computational results suggest that the induced electric field in the target area cannot be generalized without considering the morphological variability of the human brain. Moreover, there was no remarkable difference between the various coils, although focality could be improved to a certain extent by modifying the coil design (e.g., coil radius). Finally, the focality estimated by the electric field was more correlated with the magnetic vector potential than the magnetic field in a homogeneous sphere.

Evaluation method for in situ electric field in standardized human brain for different transcranial magnetic stimulation coils.

PubMed

Iwahashi, Masahiro; Gomez-Tames, Jose; Laakso, Ilkka; Hirata, Akimasa

2017-03-21

This study proposes a method to evaluate the electric field induced in the brain by transcranial magnetic stimulation (TMS) to realize focal stimulation in the target area considering the inter-subject difference of the brain anatomy. The TMS is a non-invasive technique used for treatment/diagnosis, and it works by inducing an electric field in a specific area of the brain via a coil-induced magnetic field. Recent studies that report on the electric field distribution in the brain induced by TMS coils have been limited to simplified human brain models or a small number of detailed human brain models. Until now, no method has been developed that appropriately evaluates the coil performance for a group of subjects. In this study, we first compare the magnetic field and the magnetic vector potential distributions to determine if they can be used as predictors of the TMS focality derived from the electric field distribution. Next, the hotspots of the electric field on the brain surface of ten subjects using six coils are compared. Further, decisive physical factors affecting the focality of the induced electric field by different coils are discussed by registering the computed electric field in a standard brain space for the first time, so as to evaluate coil characteristics for a large population of subjects. The computational results suggest that the induced electric field in the target area cannot be generalized without considering the morphological variability of the human brain. Moreover, there was no remarkable difference between the various coils, although focality could be improved to a certain extent by modifying the coil design (e.g., coil radius). Finally, the focality estimated by the electric field was more correlated with the magnetic vector potential than the magnetic field in a homogeneous sphere.

Using Brain Electrical Activity Mapping to Diagnose Learning Disabilities.

ERIC Educational Resources Information Center

Torello, Michael, W.; Duffy, Frank H.

1985-01-01

Cognitive neuroscience assumes that measurement of brain electrical activity should relate to cognition. Brain Electrical Activity Mapping (BEAM), a non-invasive technique, is used to record changes in activity from one brain area to another and is 80 to 90 percent successful in classifying subjects as dyslexic or normal. (MT)

Automatic detection and segmentation of brain metastases on multimodal MR images with a deep convolutional neural network.

PubMed

Charron, Odelin; Lallement, Alex; Jarnet, Delphine; Noblet, Vincent; Clavier, Jean-Baptiste; Meyer, Philippe

2018-04-01

Stereotactic treatments are today the reference techniques for the irradiation of brain metastases in radiotherapy. The dose per fraction is very high, and delivered in small volumes (diameter <1 cm). As part of these treatments, effective detection and precise segmentation of lesions are imperative. Many methods based on deep-learning approaches have been developed for the automatic segmentation of gliomas, but very little for that of brain metastases. We adapted an existing 3D convolutional neural network (DeepMedic) to detect and segment brain metastases on MRI. At first, we sought to adapt the network parameters to brain metastases. We then explored the single or combined use of different MRI modalities, by evaluating network performance in terms of detection and segmentation. We also studied the interest of increasing the database with virtual patients or of using an additional database in which the active parts of the metastases are separated from the necrotic parts. Our results indicated that a deep network approach is promising for the detection and the segmentation of brain metastases on multimodal MRI. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research.

PubMed

Kouzani, Abbas Z; Abulseoud, Osama A; Tye, Susannah J; Hosain, M D Kamal; Berk, Michael

2013-01-01

Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented.

Identification of autism spectrum disorder using deep learning and the ABIDE dataset.

PubMed

Heinsfeld, Anibal Sólon; Franco, Alexandre Rosa; Craddock, R Cameron; Buchweitz, Augusto; Meneguzzi, Felipe

2018-01-01

The goal of the present study was to apply deep learning algorithms to identify autism spectrum disorder (ASD) patients from large brain imaging dataset, based solely on the patients brain activation patterns. We investigated ASD patients brain imaging data from a world-wide multi-site database known as ABIDE (Autism Brain Imaging Data Exchange). ASD is a brain-based disorder characterized by social deficits and repetitive behaviors. According to recent Centers for Disease Control data, ASD affects one in 68 children in the United States. We investigated patterns of functional connectivity that objectively identify ASD participants from functional brain imaging data, and attempted to unveil the neural patterns that emerged from the classification. The results improved the state-of-the-art by achieving 70% accuracy in identification of ASD versus control patients in the dataset. The patterns that emerged from the classification show an anticorrelation of brain function between anterior and posterior areas of the brain; the anticorrelation corroborates current empirical evidence of anterior-posterior disruption in brain connectivity in ASD. We present the results and identify the areas of the brain that contributed most to differentiating ASD from typically developing controls as per our deep learning model.

Simultaneous in vivo recording of local brain temperature and electrophysiological signals with a novel neural probe

NASA Astrophysics Data System (ADS)

Fekete, Z.; Csernai, M.; Kocsis, K.; Horváth, Á. C.; Pongrácz, A.; Barthó, P.

2017-06-01

Objective. Temperature is an important factor for neural function both in normal and pathological states, nevertheless, simultaneous monitoring of local brain temperature and neuronal activity has not yet been undertaken. Approach. In our work, we propose an implantable, calibrated multimodal biosensor that facilitates the complex investigation of thermal changes in both cortical and deep brain regions, which records multiunit activity of neuronal populations in mice. The fabricated neural probe contains four electrical recording sites and a platinum temperature sensor filament integrated on the same probe shaft within a distance of 30 µm from the closest recording site. The feasibility of the simultaneous functionality is presented in in vivo studies. The probe was tested in the thalamus of anesthetized mice while manipulating the core temperature of the animals. Main results. We obtained multiunit and local field recordings along with measurement of local brain temperature with accuracy of 0.14 °C. Brain temperature generally followed core body temperature, but also showed superimposed fluctuations corresponding to epochs of increased local neural activity. With the application of higher currents, we increased the local temperature by several degrees without observable tissue damage between 34-39 °C. Significance. The proposed multifunctional tool is envisioned to broaden our knowledge on the role of the thermal modulation of neuronal activity in both cortical and deeper brain regions.

Does the use of thiopental provide added cerebral protection during deep hypothermic circulatory arrest?

PubMed Central

Al-Hashimi, Sara; Zaman, Mahvash; Waterworth, Paul; Bilal, Haris

2013-01-01

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Does the use of thiopental provide added cerebral protection during deep hypothermic circulatory arrest (DHCA)? Altogether, more than 62 papers were found using the reported search, of which 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Four of the seven papers used thiopental alongside other neuroprotective methods and agents. The methods included the use of ice packs to the head and core systemic hypothermia. Agents used alongside thiopental included nicardipine and mannitol. Thiopental was found to have the ability to lower oxygen consumption, where oxygen consumption was measured using the phosphocreatinine and adenosine triphosphate ratio. The neuroprotective effect of thiopental was evaluated by assessing the electrical activity of the brain during circulatory arrest, by which it was shown to be advantageous. However, other trials suggested that adding thiopental during circulatory arrest did not provide any extra protection to the brain. The timing of thiopental administration is of importance in order to gain positive outcomes, as it's ability to lower the cerebral energy state may result in unfavourable results if added before hypothermic circulatory arrest, where this may lead to an ischaemic event. We conclude that the use of thiopental during deep hypothermic circulatory arrest is beneficial, but if administered too early, it may replete the cerebral energy state before arrest and prove to be detrimental. PMID:23644730

Does the use of thiopental provide added cerebral protection during deep hypothermic circulatory arrest?

PubMed

Al-Hashimi, Sara; Zaman, Mahvash; Waterworth, Paul; Bilal, Haris

2013-08-01

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Does the use of thiopental provide added cerebral protection during deep hypothermic circulatory arrest (DHCA)? Altogether, more than 62 papers were found using the reported search, of which 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Four of the seven papers used thiopental alongside other neuroprotective methods and agents. The methods included the use of ice packs to the head and core systemic hypothermia. Agents used alongside thiopental included nicardipine and mannitol. Thiopental was found to have the ability to lower oxygen consumption, where oxygen consumption was measured using the phosphocreatinine and adenosine triphosphate ratio. The neuroprotective effect of thiopental was evaluated by assessing the electrical activity of the brain during circulatory arrest, by which it was shown to be advantageous. However, other trials suggested that adding thiopental during circulatory arrest did not provide any extra protection to the brain. The timing of thiopental administration is of importance in order to gain positive outcomes, as it's ability to lower the cerebral energy state may result in unfavourable results if added before hypothermic circulatory arrest, where this may lead to an ischaemic event. We conclude that the use of thiopental during deep hypothermic circulatory arrest is beneficial, but if administered too early, it may replete the cerebral energy state before arrest and prove to be detrimental.

Improved transcranial magnetic stimulation coil design with realistic head modeling

NASA Astrophysics Data System (ADS)

Crowther, Lawrence; Hadimani, Ravi; Jiles, David

2013-03-01

We are investigating Transcranial magnetic stimulation (TMS) as a noninvasive technique based on electromagnetic induction which causes stimulation of the neurons in the brain. TMS can be used as a pain-free alternative to conventional electroconvulsive therapy (ECT) which is still widely implemented for treatment of major depression. Development of improved TMS coils capable of stimulating subcortical regions could also allow TMS to replace invasive deep brain stimulation (DBS) which requires surgical implantation of electrodes in the brain. Our new designs allow new applications of the technique to be established for a variety of diagnostic and therapeutic applications of psychiatric disorders and neurological diseases. Calculation of the fields generated inside the head is vital for the use of this method for treatment. In prior work we have implemented a realistic head model, incorporating inhomogeneous tissue structures and electrical conductivities, allowing the site of neuronal activation to be accurately calculated. We will show how we utilize this model in the development of novel TMS coil designs to improve the depth of penetration and localization of stimulation produced by stimulator coils.

Ventromedial Hypothalamus and the Generation of Aggression

PubMed Central

Hashikawa, Yoshiko; Hashikawa, Koichi; Falkner, Annegret L.; Lin, Dayu

2017-01-01

Aggression is a costly behavior, sometimes with severe consequences including death. Yet aggression is prevalent across animal species ranging from insects to humans, demonstrating its essential role in the survival of individuals and groups. The question of how the brain decides when to generate this costly behavior has intrigued neuroscientists for over a century and has led to the identification of relevant neural substrates. Various lesion and electric stimulation experiments have revealed that the hypothalamus, an ancient structure situated deep in the brain, is essential for expressing aggressive behaviors. More recently, studies using precise circuit manipulation tools have identified a small subnucleus in the medial hypothalamus, the ventrolateral part of the ventromedial hypothalamus (VMHvl), as a key structure for driving both aggression and aggression-seeking behaviors. Here, we provide an updated summary of the evidence that supports a role of the VMHvl in aggressive behaviors. We will consider our recent findings detailing the physiological response properties of populations of VMHvl cells during aggressive behaviors and provide new understanding regarding the role of the VMHvl embedded within the larger whole-brain circuit for social sensation and action. PMID:29375329

Endoventricular Deep Brain Stimulation of the Third Ventricle: Proof of Concept and Application to Cluster Headache.

PubMed

Chabardès, Stéphan; Carron, Romain; Seigneuret, Eric; Torres, Napoleon; Goetz, Laurent; Krainik, Alexandre; Piallat, Brigitte; Pham, Pascale; David, Olivier; Giraud, Pierrick; Benabid, Alim Louis

2016-12-01

The third ventricle (3rd V) is surrounded by centers related to satiety, homeostasis, hormones, sleep, memory, and pain. Stimulation of the wall of the 3rd V could be useful to treat disorders related to dysfunction of the hypothalamus. To assess safety and efficacy of endoventricular electrical stimulation of the hypothalamus using a floating deep brain stimulation (DBS) lead laid on the floor of the 3rd V to treat refractory cluster headaches (CH). Seven patients, aged 24 to 60 years, experiencing chronic CH (mean chronic duration 5.8 ± 2.5 years) were enrolled in this pilot, prospective, open study assessing the safety and potential efficacy of chronic DBS of the 3rd V. Number of attacks was collected during baseline and was compared with those occurring at 3, 6, and 12 months postoperation. Any side effects that occurred during or after surgery were reported. Effect on mood was assessed using the Hospital Anxiety and Depression scale during baseline and at 6 and 12 months postoperation. Insertion of the lead into the posterior 3rd V and chronic stimulation was feasible and safe in all patients. The voltage ranged from 0.9 to 2.3 volts. The most common side effect was transient trembling vision during stimulation. At 12 months, 3 of 7 patients were pain free, 2 had 90% improvement, 1 of 7 had 75% improvement, and 1 of 7 was not significantly improved. This proof of concept demonstrates the feasibility, safety, and potential efficacy of 3rd V DBS using an endoventricular road that could be applied to treat various diseases involving hypothalamic areas. CCH, chronic cluster headacheCH, cluster headacheDBS, deep brain stimulationHAD, hospital anxiety depressionONS, occipital nerve stimulationPAG, periaqueductal gray matterPH, posterior hypothalamusPVG, periventricular gray matter3rd V, third ventricle.

Focus on desynchronization rather than excitability: a new strategy for intraencephalic electrical stimulation.

PubMed

Medeiros, Daniel de Castro; Moraes, Márcio Flávio Dutra

2014-09-01

Epilepsy is a severely debilitating brain disease, often associated with premature death, which has an urgent need for alternative methods of treatment. In fact, roughly 25% of patients with epilepsy do not have seizures satisfactorily controlled by pharmacological treatment, and 30% of these patients with treatment-refractory seizures are not even eligible for ablative surgery. Epilepsy is most readily identifiable by its seizures and/or paroxysmal events, mostly viewed as spontaneously recurrent and unpredictable, which are caused by stereotyped changes in neurological function associated with hyperexcitability and hypersynchronicity of the underlying neural networks. Treatment has strongly been based on the fixed goal of depressing neuronal activity, working under the veiled assumption that hyperexcitability would lead to synchronous neuronal activity and, therefore, to seizure. Over the last 20-30 years, the emergence of electrical (ES) of deep brain structures, a practicable option for treating patients with otherwise untreatable seizures, has broadened our understanding of anticonvulsant mechanisms that conceptually differ from those of pharmacological treatment. Conversely, the research on ES therapy applied to epilepsy is contributing significantly to untwine the phenomena of excitation from that of synchronization as potential target mechanisms for abolishing seizures and predicting paroxysmal events. This paper is, thus, an addendum to other reviews on the subject of ES therapy in epilepsy which focuses on the desynchronization effect ES has on epileptogenic neural networks rather than its effect on overall brain excitability. Copyright © 2014 Elsevier Inc. All rights reserved.

Methods of automated absence seizure detection, interference by stimulation, and possibilities for prediction in genetic absence models.

PubMed

van Luijtelaar, Gilles; Lüttjohann, Annika; Makarov, Vladimir V; Maksimenko, Vladimir A; Koronovskii, Alexei A; Hramov, Alexander E

2016-02-15

Genetic rat models for childhood absence epilepsy have become instrumental in developing theories on the origin of absence epilepsy, the evaluation of new and experimental treatments, as well as in developing new methods for automatic seizure detection, prediction, and/or interference of seizures. Various methods for automated off and on-line analyses of ECoG in rodent models are reviewed, as well as data on how to interfere with the spike-wave discharges by different types of invasive and non-invasive electrical, magnetic, and optical brain stimulation. Also a new method for seizure prediction is proposed. Many selective and specific methods for off- and on-line spike-wave discharge detection seem excellent, with possibilities to overcome the issue of individual differences. Moreover, electrical deep brain stimulation is rather effective in interrupting ongoing spike-wave discharges with low stimulation intensity. A network based method is proposed for absence seizures prediction with a high sensitivity but a low selectivity. Solutions that prevent false alarms, integrated in a closed loop brain stimulation system open the ways for experimental seizure control. The presence of preictal cursor activity detected with state of the art time frequency and network analyses shows that spike-wave discharges are not caused by sudden and abrupt transitions but that there are detectable dynamic events. Their changes in time-space-frequency characteristics might yield new options for seizure prediction and seizure control. Copyright © 2015 Elsevier B.V. All rights reserved.

[Abscess at the implant site following apical parodontitis. Hardware-related complications of deep brain stimulation].

PubMed

Sixel-Döring, F; Trenkwalder, C; Kappus, C; Hellwig, D

2006-08-01

Deep brain stimulation of the subthalamic nucleus is an important treatment option for advanced stages of idiopathic Parkinson's disease, leading to significant improvement of motor symptoms in suited patients. Hardware-related complications such as technical malfunction, skin erosion, and infections however cause patient discomfort and additional expense. The patient presented here suffered a putrid infection of the impulse generator site following only local dental treatment of apical parodontitis. Therefore, prophylactic systemic antibiotic treatment is recommended for patients with implanted deep brain stimulation devices in case of operations, dental procedures, or infectious disease.

Linear-array based full-view high-resolution photoacoustic computed tomography of whole mouse brain functions in vivo

NASA Astrophysics Data System (ADS)

Li, Lei; Zhang, Pengfei; Wang, Lihong V.

2018-02-01

Photoacoustic computed tomography (PACT) is a non-invasive imaging technique offering high contrast, high resolution, and deep penetration in biological tissues. We report a photoacoustic computed tomography (PACT) system equipped with a high frequency linear array for anatomical and functional imaging of the mouse whole brain. The linear array was rotationally scanned in the coronal plane to achieve the full-view coverage. We investigated spontaneous neural activities in the deep brain by monitoring the hemodynamics and observed strong interhemispherical correlations between contralateral regions, both in the cortical layer and in the deep regions.

Brain networks modulated by subthalamic nucleus deep brain stimulation.

PubMed

Accolla, Ettore A; Herrojo Ruiz, Maria; Horn, Andreas; Schneider, Gerd-Helge; Schmitz-Hübsch, Tanja; Draganski, Bogdan; Kühn, Andrea A

2016-09-01

Deep brain stimulation of the subthalamic nucleus is an established treatment for the motor symptoms of Parkinson's disease. Given the frequent occurrence of stimulation-induced affective and cognitive adverse effects, a better understanding about the role of the subthalamic nucleus in non-motor functions is needed. The main goal of this study is to characterize anatomical circuits modulated by subthalamic deep brain stimulation, and infer about the inner organization of the nucleus in terms of motor and non-motor areas. Given its small size and anatomical intersubject variability, functional organization of the subthalamic nucleus is difficult to investigate in vivo with current methods. Here, we used local field potential recordings obtained from 10 patients with Parkinson's disease to identify a subthalamic area with an analogous electrophysiological signature, namely a predominant beta oscillatory activity. The spatial accuracy was improved by identifying a single contact per macroelectrode for its vicinity to the electrophysiological source of the beta oscillation. We then conducted whole brain probabilistic tractography seeding from the previously identified contacts, and further described connectivity modifications along the macroelectrode's main axis. The designated subthalamic 'beta' area projected predominantly to motor and premotor cortical regions additional to connections to limbic and associative areas. More ventral subthalamic areas showed predominant connectivity to medial temporal regions including amygdala and hippocampus. We interpret our findings as evidence for the convergence of different functional circuits within subthalamic nucleus' portions deemed to be appropriate as deep brain stimulation target to treat motor symptoms in Parkinson's disease. Potential clinical implications of our study are illustrated by an index case where deep brain stimulation of estimated predominant non-motor subthalamic nucleus induced hypomanic behaviour. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Near-infrared deep brain stimulation via upconversion nanoparticle–mediated optogenetics

NASA Astrophysics Data System (ADS)

Chen, Shuo; Weitemier, Adam Z.; Zeng, Xiao; He, Linmeng; Wang, Xiyu; Tao, Yanqiu; Huang, Arthur J. Y.; Hashimotodani, Yuki; Kano, Masanobu; Iwasaki, Hirohide; Parajuli, Laxmi Kumar; Okabe, Shigeo; Teh, Daniel B. Loong; All, Angelo H.; Tsutsui-Kimura, Iku; Tanaka, Kenji F.; Liu, Xiaogang; McHugh, Thomas J.

2018-02-01

Optogenetics has revolutionized the experimental interrogation of neural circuits and holds promise for the treatment of neurological disorders. It is limited, however, because visible light cannot penetrate deep inside brain tissue. Upconversion nanoparticles (UCNPs) absorb tissue-penetrating near-infrared (NIR) light and emit wavelength-specific visible light. Here, we demonstrate that molecularly tailored UCNPs can serve as optogenetic actuators of transcranial NIR light to stimulate deep brain neurons. Transcranial NIR UCNP-mediated optogenetics evoked dopamine release from genetically tagged neurons in the ventral tegmental area, induced brain oscillations through activation of inhibitory neurons in the medial septum, silenced seizure by inhibition of hippocampal excitatory cells, and triggered memory recall. UCNP technology will enable less-invasive optical neuronal activity manipulation with the potential for remote therapy.

The habenula in neurosurgery for depression: A convergence of functional neuroanatomy, psychiatry and imaging.

PubMed

Skandalakis, Georgios P; Koutsarnakis, Christos; Kalyvas, Aristotelis V; Skandalakis, Panagiotis; Johnson, Elizabeth O; Stranjalis, George

2018-05-05

The habenula is a small, mostly underrated structure in the pineal region. Multidisciplinary findings demonstrate an underlying complex connectivity of the habenula with the rest of the brain, subserving its major role in normal behavior and the pathophysiology of depression. These findings suggest the potential application of "habenular psychosurgery" in the treatment of mental disorders. The remission of two patients with treatment-resistant major depression treated with deep brain stimulation of the habenula supported the hypothesis that the habenula is an effective target for deep brain stimulation and initiated a surge of basic science research. This review aims to assess the viability of the deep brain stimulation of the habenula as a treatment option for treatment resistant depression. PubMed and the Cochrane Library databases were searched with no chronological restrictions for the identification of relevant articles. The results of this review are presented in a narrative form describing the functional neuroanatomy of the human habenula, its implications in major depression, findings of electrode implantation of this region and findings of deep brain stimulation of the habenula for the treatment of depression. Data assessing the hypothesis are scarce. Nonetheless, findings highlight the major role of the habenula in normal, as well as in pathological brain function, particularly in depression disorders. Moreover, findings of studies utilizing electrode implantation in the region of the habenula underscore our growing realization that research in neuroscience and deep brain stimulation complement each other in a reciprocal relationship; they are as self-reliant, as much as they depend on each other. Copyright © 2018. Published by Elsevier B.V.

Electrical stimulation in the treatment of pain.

PubMed

Rushton, David N

2002-05-20

To review the published literature concerning the treatment of painful conditions using devices that deliver electrical stimulation to nervous structures. The review briefly surveys the results obtained using surface electrodes ("TENS") as well as implanted devices. The method used is a critical review of the important published literature up to mid-1999. References were obtained using Medline and the keywords "pain", together with "electrical", "stimulation", "neurostimulation" or "TENS". Electrical stimulation has been found to be of potential benefit in the management of a range of painful conditions. Adequately controlled trials of electrical stimulation are often difficult to achieve. Implanted devices tend to be used in the more severe intractable pain conditions. It is likely that there is more than one mechanism of action. The mechanisms of action are however still often poorly understood, even though historically theoretical and experimental advances in the understanding of pain mechanisms prompted the development of clinical systems and the institution of clinical studies. TENS has proved to be remarkably safe, and provides significant analgesia in about half of patients experiencing moderate predictable pain. Implanted devices can be more effective, but they carry a risk of device failure, implant infection or surgical complication, and are reserved for the more severe intractable chronic pains. The main implanted devices used clinically are the spinal cord stimulator and the deep brain stimulator.

Electrical management of neurogenic lower urinary tract disorders.

PubMed

Joussain, C; Denys, P

2015-09-01

Management of lower urinary tract dysfunction (LUTD) in neurological diseases remains a priority because it leads to many complications such as incontinence, renal failure and decreased quality of life. A pharmacological approach remains the first-line treatment for patients with neurogenic LUTD, but electrical stimulation is a well-validated and recommended second-line treatment. However, clinicians must be aware of the indications, advantages and side effects of the therapy. This report provides an update on the 2 main electrical stimulation therapies for neurogenic LUTD - inducing direct bladder contraction with the Brindley procedure and modulating LUT physiology (sacral neuromodulation, tibial posterior nerve stimulation or pudendal nerve stimulation). We also describe the indications of these therapies for neurogenic LUTD, following international guidelines, as illustrated by their efficacy in patients with neurologic disorders. Electrical stimulation could be proposed for neurogenic LUTD as second-line treatment after failure of oral pharmacologic approaches. Nevertheless, further investigations are needed for a better understanding of the mechanisms of action of these techniques and to confirm their efficacy. Other electrical investigations, such as deep-brain stimulation and repetitive transcranial magnetic stimulation, or improved sacral anterior root stimulation, which could be associated with non-invasive and highly specific deafferentation of posterior roots, may open new fields in the management of neurogenic LUTD. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Stereotactically Standard Areas: Applied Mathematics in the Service of Brain Targeting in Deep Brain Stimulation.

PubMed

Mavridis, Ioannis N

2017-12-11

The concept of stereotactically standard areas (SSAs) within human brain nuclei belongs to the knowledge of the modern field of stereotactic brain microanatomy. These are areas resisting the individual variability of the nuclear location in stereotactic space. This paper summarizes the current knowledge regarding SSAs. A mathematical formula of SSAs was recently invented, allowing for their robust, reproducible, and accurate application to laboratory studies and clinical practice. Thus, SSAs open new doors for the application of stereotactic microanatomy to highly accurate brain targeting, which is mainly useful for minimally invasive neurosurgical procedures, such as deep brain stimulation.

Current steering to activate targeted neural pathways during deep brain stimulation of the subthalamic region

PubMed Central

Chaturvedi, Ashutosh; Foutz, Thomas J.; McIntyre, Cameron C.

2012-01-01

Deep brain stimulation (DBS) has steadily evolved into an established surgical therapy for numerous neurological disorders, most notably Parkinson’s disease (PD). Traditional DBS technology relies on voltage-controlled stimulation with a single source; however, recent engineering advances are providing current-controlled devices with multiple independent sources. These new stimulators deliver constant current to the brain tissue, irrespective of impedance changes that occur around the electrode, and enable more specific steering of current towards targeted regions of interest. In this study, we examined the impact of current steering between multiple electrode contacts to directly activate three distinct neural populations in the subthalamic region commonly stimulated for the treatment of PD: projection neurons of the subthalamic nucleus (STN), globus pallidus internus (GPi) fibers of the lenticular fasiculus, and internal capsule (IC) fibers of passage. We used three-dimensional finite element electric field models, along with detailed multi-compartment cable models of the three neural populations to determine their activations using a wide range of stimulation parameter settings. Our results indicate that selective activation of neural populations largely depends on the location of the active electrode(s). Greater activation of the GPi and STN populations (without activating any side-effect related IC fibers) was achieved by current steering with multiple independent sources, compared to a single current source. Despite this potential advantage, it remains to be seen if these theoretical predictions result in a measurable clinical effect that outweighs the added complexity of the expanded stimulation parameter search space generated by the more flexible technology. PMID:22277548

CMOS Image Sensor and System for Imaging Hemodynamic Changes in Response to Deep Brain Stimulation.

PubMed

Zhang, Xiao; Noor, Muhammad S; McCracken, Clinton B; Kiss, Zelma H T; Yadid-Pecht, Orly; Murari, Kartikeya

2016-06-01

Deep brain stimulation (DBS) is a therapeutic intervention used for a variety of neurological and psychiatric disorders, but its mechanism of action is not well understood. It is known that DBS modulates neural activity which changes metabolic demands and thus the cerebral circulation state. However, it is unclear whether there are correlations between electrophysiological, hemodynamic and behavioral changes and whether they have any implications for clinical benefits. In order to investigate these questions, we present a miniaturized system for spectroscopic imaging of brain hemodynamics. The system consists of a 144 ×144, [Formula: see text] pixel pitch, high-sensitivity, analog-output CMOS imager fabricated in a standard 0.35 μm CMOS process, along with a miniaturized imaging system comprising illumination, focusing, analog-to-digital conversion and μSD card based data storage. This enables stand alone operation without a computer, nor electrical or fiberoptic tethers. To achieve high sensitivity, the pixel uses a capacitive transimpedance amplifier (CTIA). The nMOS transistors are in the pixel while pMOS transistors are column-parallel, resulting in a fill factor (FF) of 26%. Running at 60 fps and exposed to 470 nm light, the CMOS imager has a minimum detectable intensity of 2.3 nW/cm(2) , a maximum signal-to-noise ratio (SNR) of 49 dB at 2.45 μW/cm(2) leading to a dynamic range (DR) of 61 dB while consuming 167 μA from a 3.3 V supply. In anesthetized rats, the system was able to detect temporal, spatial and spectral hemodynamic changes in response to DBS.

The effects of deep level traps on the electrical properties of semi-insulating CdZnTe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zha, Gangqiang; Yang, Jian; Xu, Lingyan

2014-01-28

Deep level traps have considerable effects on the electrical properties and radiation detection performance of high resistivity CdZnTe. A deep-trap model for high resistivity CdZnTe was proposed in this paper. The high resistivity mechanism and the electrical properties were analyzed based on this model. High resistivity CdZnTe with high trap ionization energy E{sub t} can withstand high bias voltages. The leakage current is dependent on both the deep traps and the shallow impurities. The performance of a CdZnTe radiation detector will deteriorate at low temperatures, and the way in which sub-bandgap light excitation could improve the low temperature performance canmore » be explained using the deep trap model.« less

'Being in it together': living with a partner receiving deep brain stimulation for advanced Parkinson's disease--a hermeneutic phenomenological study.

PubMed

Haahr, Anita; Kirkevold, Marit; Hall, Elisabeth O C; Østergaard, Karen

2013-02-01

This article is a report of an exploration of the lived experience of being a spouse to a person living with advanced Parkinson's disease, before and during the first year of deep brain stimulation. Parkinson's disease is a chronic progressive neurodegenerative disease. It has a profound impact on the everyday life for patients and spouses. Deep brain stimulation is offered with the aim of reducing symptoms of Parkinson's disease. The treatment is known to improve quality of life for patients, but little is known of how spouses experience life following their partners' treatment. A longitudinal interview study with a hermeneutic phenomenological approach. Ten spouses were included in the study. Data were gathered in 2007-2008, through qualitative in-depth interviews with spouses once before and three times during the first year of their partners' treatment with Deep Brain Stimulation. Data collection and data analysis were influenced by the hermeneutic phenomenological methodology of van Manen. The uniting theme 'Solidarity - the base for joined responsibility and concern' was the foundation for the relationship between spouses and their partners. Before treatment, the theme 'Living in partnership' was dominant. After treatment two dichotomous courses were described 'A sense of freedom embracing life' and 'The challenge of changes and constraint'. Spouses are deeply involved in their partners' illness and their experience of life is highly affected by their partners' illness, both before and after deep brain stimulation. The relationship is founded on solidarity and responsibility, which emphasizes spouses' need to be informed and involved in the process following Deep Brain Stimulation. © 2012 Blackwell Publishing Ltd.

Effects of deep brain stimulation in dyskinetic cerebral palsy: a meta-analysis.

PubMed

Koy, Anne; Hellmich, Martin; Pauls, K Amande M; Marks, Warren; Lin, Jean-Pierre; Fricke, Oliver; Timmermann, Lars

2013-05-01

Secondary dystonia encompasses a heterogeneous group with different etiologies. Cerebral palsy is the most common cause. Pharmacological treatment is often unsatisfactory. There are only limited data on the therapeutic outcomes of deep brain stimulation in dyskinetic cerebral palsy. The published literature regarding deep brain stimulation and secondary dystonia was reviewed in a meta-analysis to reevaluate the effect on cerebral palsy. The Burke-Fahn-Marsden Dystonia Rating Scale movement score was chosen as the primary outcome measure. Outcome over time was evaluated and summarized by mixed-model repeated-measures analysis, paired Student t test, and Pearson's correlation coefficient. Twenty articles comprising 68 patients with cerebral palsy undergoing deep brain stimulation assessed by the Burke-Fahn-Marsden Dystonia Rating Scale were identified. Most articles were case reports reflecting great variability in the score and duration of follow-up. The mean Burke-Fahn-Marsden Dystonia Rating Scale movement score was 64.94 ± 25.40 preoperatively and dropped to 50.5 ± 26.77 postoperatively, with a mean improvement of 23.6% (P < .001) at a median follow-up of 12 months. The mean Burke-Fahn-Marsden Dystonia Rating Scale disability score was 18.54 ± 6.15 preoperatively and 16.83 ± 6.42 postoperatively, with a mean improvement of 9.2% (P < .001). There was a significant negative correlation between severity of dystonia and clinical outcome (P < .05). Deep brain stimulation can be an effective treatment option for dyskinetic cerebral palsy. In view of the heterogeneous data, a prospective study with a large cohort of patients in a standardized setting with a multidisciplinary approach would be helpful in further evaluating the role of deep brain stimulation in cerebral palsy. © 2013 Movement Disorder Society. Copyright © 2013 Movement Disorder Society.

EKG-based detection of deep brain stimulation in fMRI studies.

PubMed

Fiveland, Eric; Madhavan, Radhika; Prusik, Julia; Linton, Renee; Dimarzio, Marisa; Ashe, Jeffrey; Pilitsis, Julie; Hancu, Ileana

2018-04-01

To assess the impact of synchronization errors between the assumed functional MRI paradigm timing and the deep brain stimulation (DBS) on/off cycling using a custom electrocardiogram-based triggering system METHODS: A detector for measuring and predicting the on/off state of cycling deep brain stimulation was developed and tested in six patients in office visits. Three-electrode electrocardiogram measurements, amplified by a commercial bio-amplifier, were used as input for a custom electronics box (e-box). The e-box transformed the deep brain stimulation waveforms into transistor-transistor logic pulses, recorded their timing, and propagated it in time. The e-box was used to trigger task-based deep brain stimulation functional MRI scans in 5 additional subjects; the impact of timing accuracy on t-test values was investigated in a simulation study using the functional MRI data. Following locking to each patient's individual waveform, the e-box was shown to predict stimulation onset with an average absolute error of 112 ± 148 ms, 30 min after disconnecting from the patients. The subsecond accuracy of the e-box in predicting timing onset is more than adequate for our slow varying, 30-/30-s on/off stimulation paradigm. Conversely, the experimental deep brain stimulation onset prediction accuracy in the absence of the e-box, which could be off by as much as 4 to 6 s, could significantly decrease activation strength. Using this detector, stimulation can be accurately synchronized to functional MRI acquisitions, without adding any additional hardware in the MRI environment. Magn Reson Med 79:2432-2439, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Effects of electrode gap and electric current on chlorine generation of electrolyzed deep ocean water.

PubMed

Hsu, Guoo-Shyng Wang; Hsu, Shun-Yao

2018-04-01

Electrolyzed water is a sustainable disinfectant, which can comply with food safety regulations and is environmental friendly. A two-factor central composite design was adopted for studying the effects of electrode gap and electric current on chlorine generation efficiency of electrolyzed deep ocean water. Deep ocean water was electrolyzed in a glass electrolyzing cell equipped with platinum-plated titanium anode and cathode in a constant-current operation mode. Results showed that current density, chlorine concentration, and electrolyte temperature increased with electric current, while electric efficiency decreased with electric current and electrode gap. An electrode gap of less than 11.7 mm, and a low electric current appeared to be a more energy efficient design and operation condition for the electrolysis system. Copyright © 2017. Published by Elsevier B.V.

Flexible deep brain neural probes based on a parylene tube structure

NASA Astrophysics Data System (ADS)

Zhao, Zhiguo; Kim, Eric; Luo, Hao; Zhang, Jinsheng; Xu, Yong

2018-01-01

Most microfabricated neural probes have limited shank length, which prevents them from reaching many deep brain structures. This paper reports deep brain neural probes with ultra-long penetrating shanks based on a simple but novel parylene tube structure. The mechanical strength of the parylene tube shank is temporarily enhanced during implantation by inserting a metal wire. The metal wire can be removed after implantation, making the implanted probe very flexible and thus minimizing the stress caused by micromotions of brain tissues. Optogenetic stimulation and chemical delivery capabilities can be potentially integrated by taking advantage of the tube structure. Single-shank prototypes with a shank length of 18.2 mm have been developed. The microfabrication process comprises of deep reactive ion etching (DRIE) of silicon, parylene conformal coating/refilling, and XeF2 isotropic silicon etching. In addition to bench-top insertion characterization, the functionality of developed probes has been preliminarily demonstrated by implanting into the amygdala of a rat and recording neural signals.

Scientific and ethical issues related to deep brain stimulation for disorders of mood, behavior, and thought.

PubMed

Rabins, Peter; Appleby, Brian S; Brandt, Jason; DeLong, Mahlon R; Dunn, Laura B; Gabriëls, Loes; Greenberg, Benjamin D; Haber, Suzanne N; Holtzheimer, Paul E; Mari, Zoltan; Mayberg, Helen S; McCann, Evelyn; Mink, Sallie P; Rasmussen, Steven; Schlaepfer, Thomas E; Vawter, Dorothy E; Vitek, Jerrold L; Walkup, John; Mathews, Debra J H

2009-09-01

A 2-day consensus conference was held to examine scientific and ethical issues in the application of deep brain stimulation for treating mood and behavioral disorders, such as major depression, obsessive-compulsive disorder, and Tourette syndrome. The primary objectives of the conference were to (1) establish consensus among participants about the design of future clinical trials of deep brain stimulation for disorders of mood, behavior, and thought and (2) develop standards for the protection of human subjects participating in such studies. Conference participants identified 16 key points for guiding research in this growing field. The adoption of the described guidelines would help to protect the safety and rights of research subjects who participate in clinical trials of deep brain stimulation for disorders of mood, behavior, and thought and have further potential to benefit other stakeholders in the research process, including clinical researchers and device manufactures. That said, the adoption of the guidelines will require broad and substantial commitment from many of these same stakeholders.

Primary experimental study on safety of deep brain stimulation in RF electromagnetic field.

PubMed

Jun, Xu; Luming, Li; Hongwei, Hao

2009-01-01

With the rapid growth of clinical application of Deep Brain Stimulation, its safety and functional concern in the electromagnetic field, another pollution becoming much more serious, has become more and more significant. Meanwhile, the measuring standards on Electromagnetic Compatibility (EMC) for DBS are still incomplete. Particularly, the knowledge of the electromagnetic field induced signals on the implanted lead is ignorant while some informal reports some side effects. This paper briefly surmised the status of EMC standards on implantable medical devices. Based on the EMC experiments of DBS device we developed, two experiments for measuring the induced voltage of the deep brain stimulator in RF electromagnetic field were reported. The measured data showed that the induced voltage in some frequency was prominent, for example over 2V. As a primary research, we think these results would be significant to cause researcher to pay more attention to the EMC safety problem and biological effects of the induced voltage in deep brain stimulation and other implantable devices.

Body and brain temperature coupling: the critical role of cerebral blood flow

PubMed Central

Ackerman, Joseph J. H.; Yablonskiy, Dmitriy A.

2010-01-01

Direct measurements of deep-brain and body-core temperature were performed on rats to determine the influence of cerebral blood flow (CBF) on brain temperature regulation under static and dynamic conditions. Static changes of CBF were achieved using different anesthetics (chloral hydrate, CH; α-chloralose, αCS; and isoflurane, IF) with αCS causing larger decreases in CBF than CH and IF; dynamic changes were achieved by inducing transient hypercapnia (5% CO2 in 40% O2 and 55% N2). Initial deep-brain/body-core temperature differentials were anesthetic-type dependent with the largest differential observed with rats under αCS anesthesia (ca. 2°C). Hypercapnia induction raised rat brain temperature under all three anesthesia regimes, but by different anesthetic-dependent amounts correlated with the initial differentials—αCS anesthesia resulted in the largest brain temperature increase (0.32 ± 0.08°C), while CH and IF anesthesia lead to smaller increases (0.12 ± 0.03 and 0.16 ± 0.05°C, respectively). The characteristic temperature transition time for the hypercapnia-induced temperature increase was 2–3 min under CH and IF anesthesia and ~4 min under αCS anesthesia. We conclude that both, the deep-brain/body-core temperature differential and the characteristic temperature transition time correlate with CBF: a lower CBF promotes higher deep-brain/body-core temperature differentials and, upon hypercapnia challenge, longer characteristic transition times to increased temperatures. PMID:19277681

Body and brain temperature coupling: the critical role of cerebral blood flow.

PubMed

Zhu, Mingming; Ackerman, Joseph J H; Yablonskiy, Dmitriy A

2009-08-01

Direct measurements of deep-brain and body-core temperature were performed on rats to determine the influence of cerebral blood flow (CBF) on brain temperature regulation under static and dynamic conditions. Static changes of CBF were achieved using different anesthetics (chloral hydrate, CH; alpha-chloralose, alphaCS; and isoflurane, IF) with alphaCS causing larger decreases in CBF than CH and IF; dynamic changes were achieved by inducing transient hypercapnia (5% CO(2) in 40% O(2) and 55% N(2)). Initial deep-brain/body-core temperature differentials were anesthetic-type dependent with the largest differential observed with rats under alphaCS anesthesia (ca. 2 degrees C). Hypercapnia induction raised rat brain temperature under all three anesthesia regimes, but by different anesthetic-dependent amounts correlated with the initial differentials--alphaCS anesthesia resulted in the largest brain temperature increase (0.32 +/- 0.08 degrees C), while CH and IF anesthesia lead to smaller increases (0.12 +/- 0.03 and 0.16 +/- 0.05 degrees C, respectively). The characteristic temperature transition time for the hypercapnia-induced temperature increase was 2-3 min under CH and IF anesthesia and approximately 4 min under alphaCS anesthesia. We conclude that both, the deep-brain/body-core temperature differential and the characteristic temperature transition time correlate with CBF: a lower CBF promotes higher deep-brain/body-core temperature differentials and, upon hypercapnia challenge, longer characteristic transition times to increased temperatures.

[The Dual Nature of the Electrical Signals of the Brain (Electrical and Electrochemical) Which Were Recorded With the Help Polarizable Electrodes From Inert Metals].

PubMed

Dubinin, A G; Reutov, V P; Svinov, M M; Troshin, G I; Shvets-Teneta-Gurii, T B

2015-01-01

In the modern neurophysiology opinion was confirmed that the electrical signals of the brain in the frequency band from DC to electroencephalogram recorded with metallic conductors of inert metal implanted in the brain are formed solely by changes in the electric field of the brain. This paper presents a review of the literature and our own data, according to which the formation of these signals involves two factors. One factor is a change in the charge of the electric double layer electrode having a capacitor property and change the value of its charge with changes in the electric field volume conductor--the brain. Another factor is an electrochemical signal is defined by local changes in the redox potential (E) neuronal-glial populations surrounding the electrode. The paper provides an overviews the electrical and electrochemical properties of the electrodes of the inert metals used in electrophysiology. It is shown that each of these factors has the characteristic parameters over time and amplitude. The data of own studies of local changes in E cortex accompanying brain's response to the implantation of electrodes in the brain's cortex, the natural behavior of animals in the wake-sleep, integrative brain function and effect of pharmacological agents. These results give evidence of the highly informative study of local changes in brain E in order to study energy metabolism in the brain of waking animals, and lay the foundation for the study of local changes in brain energy metabolism in free animal behavior.

Regional anatomy of the pedunculopontine nucleus: relevance for deep brain stimulation.

PubMed

Fournier-Gosselin, Marie-Pierre; Lipsman, Nir; Saint-Cyr, Jean A; Hamani, Clement; Lozano, Andres M

2013-09-01

The pedunculopontine nucleus (PPN) is currently being investigated as a potential deep brain stimulation target to improve gait and posture in Parkinson's disease. This review examines the complex anatomy of the PPN region and suggests a functional mapping of the surrounding nuclei and fiber tracts that may serve as a guide to a more accurate placement of electrodes while avoiding potentially adverse effects. The relationships of the PPN were examined in different human brain atlases. Schematic representations of those structures in the vicinity of the PPN were generated and correlated with their potential stimulation effects. By providing a functional map and representative schematics of the PPN region, we hope to optimize the placement of deep brain stimulation electrodes, thereby maximizing safety and clinical efficacy. © 2013 International Parkinson and Movement Disorder Society.

Camptocormia and deep brain stimulation: The interesting overlapping etiologies and the therapeutic role of subthalamic nucleus-deep brain stimulation in Parkinson disease with camptocormia.

PubMed

Ekmekci, Hakan; Kaptan, Hulagu

2016-01-01

Camptocormia is known as "bent spine syndrome" and defined as a forward hyperflexion. The most common etiologic factor is related with the movement disorders, mainly in Parkinson's disease (PD). We present the case of a 51-year-old woman who has been followed with PD for the last 10 years, and also under the therapy for PD. An unappreciated correlation low back pain with camptocormia developed. She underwent deep brain stimulation (DBS) in the subthalamic nucleus bilaterally and improved her bending posture. The relationship between the DBS and camptocormia is discussed in this unique condition.

Deep Brain Stimulation for Essential Vocal Tremor: A Technical Report.

PubMed

Ho, Allen L; Choudhri, Omar; Sung, C Kwang; DiRenzo, Elizabeth E; Halpern, Casey H

2015-03-01

Essential vocal tremor (EVT) is the presence of a tremulous voice that is commonly associated with essential tremor. Patients with EVT often report a necessary increase in vocal effort that significantly worsens with stress and anxiety and can significantly impact quality of life despite optimal medical and behavioral treatment options. Deep brain stimulation (DBS) has been proposed as an effective therapy for vocal tremor, but very few studies exist in the literature that comprehensively evaluate the efficacy of DBS for specifically addressing EVT. We present a technical report on our multidisciplinary, comprehensive operative methodology for treatment of EVT with frameless, awake deep brain stimulation (DBS).

Deep Brain Stimulation for Essential Vocal Tremor: A Technical Report

PubMed Central

Choudhri, Omar; Sung, C. Kwang; DiRenzo, Elizabeth E; Halpern, Casey H

2015-01-01

Essential vocal tremor (EVT) is the presence of a tremulous voice that is commonly associated with essential tremor. Patients with EVT often report a necessary increase in vocal effort that significantly worsens with stress and anxiety and can significantly impact quality of life despite optimal medical and behavioral treatment options. Deep brain stimulation (DBS) has been proposed as an effective therapy for vocal tremor, but very few studies exist in the literature that comprehensively evaluate the efficacy of DBS for specifically addressing EVT. We present a technical report on our multidisciplinary, comprehensive operative methodology for treatment of EVT with frameless, awake deep brain stimulation (DBS). PMID:26180680

Perylene-diimide-based nanoparticles as highly efficient photoacoustic agents for deep brain tumor imaging in living mice

DOE PAGES

Fan, Quli; Cheng, Kai; Yang, Zhen; ...

2014-11-06

In order to promote preclinical and clinical applications of photoacoustic imaging, novel photoacoustic contrast agents are highly desired for molecular imaging of diseases, especially for deep tumor imaging. In this paper, perylene-3,4,9,10-tetracarboxylic diiimide-based near-infrared-absorptive organic nanoparticles are reported as an efficient agent for photoacoustic imaging of deep brain tumors in living mice with enhanced permeability and retention effect

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization

PubMed Central

Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P.; Johnson, G. Allan

2015-01-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved 3D reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate accurate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. PMID:26043869

Subthalamic Nucleus Deep Brain Stimulation Changes Velopharyngeal Control in Parkinson's Disease

ERIC Educational Resources Information Center

Hammer, Michael J.; Barlow, Steven M.; Lyons, Kelly E.; Pahwa, Rajesh

2011-01-01

Purpose: Adequate velopharyngeal control is essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on velopharyngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of velopharyngeal…

Cognitive Functioning in Children with Pantothenate-Kinase-Associated Neurodegeneration Undergoing Deep Brain Stimulation

ERIC Educational Resources Information Center

Mahoney, Rachel; Selway, Richard; Lin, Jean-Pierre

2011-01-01

Aim: To examine the cognitive functioning of young people with pantothenate-kinase-associated neurodegeneration (PKAN) after pallidal deep brain stimulation (DBS). PKAN is characterized by progressive generalized dystonia and has historically been associated with cognitive decline. With growing evidence that DBS can improve motor function in…

The Effect of Deep Brain Stimulation on the Speech Motor System

ERIC Educational Resources Information Center

Mücke, Doris; Becker, Johannes; Barbe, Michael T.; Meister, Ingo; Liebhart, Lena; Roettger, Timo B.; Dembek, Till; Timmermann, Lars; Grice, Martine

2014-01-01

Purpose: Chronic deep brain stimulation of the nucleus ventralis intermedius is an effective treatment for individuals with medication-resistant essential tremor. However, these individuals report that stimulation has a deleterious effect on their speech. The present study investigates one important factor leading to these effects: the…

Affect of deep brain stimulation on limb paresis after stroke.

PubMed

Phillips, N I; Bhakta, B B

2000-07-15

A deep brain stimulator was implanted in the periventricular grey matter of the third ventricle for pain after stroke in a man aged 48 years. As well as a beneficial analgesic effect, the patient reported improved function in the contralateral paretic arm, which was confirmed on formal testing.

Referred pain and cutaneous responses from deep tissue electrical pain stimulation in the groin.

PubMed

Aasvang, E K; Werner, M U; Kehlet, H

2015-08-01

Persistent postherniotomy pain is located around the scar and external inguinal ring and is often described as deep rather than cutaneous, with frequent complaints of pain in adjacent areas. Whether this pain is due to local pathology or referred/projected pain is unknown, hindering mechanism-based treatment. Deep tissue electrical pain stimulation by needle electrodes in the right groin (rectus muscle, ilioinguinal/iliohypogastric nerve and perispermatic cord) was combined with assessment of referred/projected pain and the cutaneous heat pain threshold (HPT) at three prespecified areas (both groins and the lower right arm) in 19 healthy subjects. The assessment was repeated 10 days later to assess the reproducibility of individual responses. Deep electrical stimulation elicited pain at the stimulation site in all subjects, and in 15 subjects, pain from areas outside the stimulation area was reported, with 90-100% having the same response on both days, depending on the location. Deep pain stimulation significantly increased the cutaneous HPT (P<0.014). Individual HPT responses before and during deep electrical pain stimulation were significantly correlated (ρ>0.474, P≤0.040) at the two test days for the majority of test areas. Our results corroborate a systematic relationship between deep pain and changes in cutaneous nociception. The individual referred/projected pain patterns and cutaneous responses are variable, but reproducible, supporting individual differences in anatomy and sensory processing. Future studies investigating the responses to deep tissue electrical stimulation in persistent postherniotomy pain patients may advance our understanding of underlying pathophysiological mechanisms and strategies for treatment and prevention. ClinicalTrials.gov (NCT01701427). © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Three dimensional amorphous silicon/microcrystalline silicon solar cells

DOEpatents

Kaschmitter, James L.

1996-01-01

Three dimensional deep contact amorphous silicon/microcrystalline silicon (a-Si/.mu.c-Si) solar cells which use deep (high aspect ratio) p and n contacts to create high electric fields within the carrier collection volume material of the cell. The deep contacts are fabricated using repetitive pulsed laser doping so as to create the high aspect p and n contacts. By the provision of the deep contacts which penetrate the electric field deep into the material where the high strength of the field can collect many of the carriers, thereby resulting in a high efficiency solar cell.

Three dimensional amorphous silicon/microcrystalline silicon solar cells

DOEpatents

Kaschmitter, J.L.

1996-07-23

Three dimensional deep contact amorphous silicon/microcrystalline silicon (a-Si/{micro}c-Si) solar cells are disclosed which use deep (high aspect ratio) p and n contacts to create high electric fields within the carrier collection volume material of the cell. The deep contacts are fabricated using repetitive pulsed laser doping so as to create the high aspect p and n contacts. By the provision of the deep contacts which penetrate the electric field deep into the material where the high strength of the field can collect many of the carriers, thereby resulting in a high efficiency solar cell. 4 figs.

Concussion classification via deep learning using whole-brain white matter fiber strains

PubMed Central

Cai, Yunliang; Wu, Shaoju; Zhao, Wei; Li, Zhigang; Wu, Zheyang

2018-01-01

Developing an accurate and reliable injury predictor is central to the biomechanical studies of traumatic brain injury. State-of-the-art efforts continue to rely on empirical, scalar metrics based on kinematics or model-estimated tissue responses explicitly pre-defined in a specific brain region of interest. They could suffer from loss of information. A single training dataset has also been used to evaluate performance but without cross-validation. In this study, we developed a deep learning approach for concussion classification using implicit features of the entire voxel-wise white matter fiber strains. Using reconstructed American National Football League (NFL) injury cases, leave-one-out cross-validation was employed to objectively compare injury prediction performances against two baseline machine learning classifiers (support vector machine (SVM) and random forest (RF)) and four scalar metrics via univariate logistic regression (Brain Injury Criterion (BrIC), cumulative strain damage measure of the whole brain (CSDM-WB) and the corpus callosum (CSDM-CC), and peak fiber strain in the CC). Feature-based machine learning classifiers including deep learning, SVM, and RF consistently outperformed all scalar injury metrics across all performance categories (e.g., leave-one-out accuracy of 0.828–0.862 vs. 0.690–0.776, and .632+ error of 0.148–0.176 vs. 0.207–0.292). Further, deep learning achieved the best cross-validation accuracy, sensitivity, AUC, and .632+ error. These findings demonstrate the superior performances of deep learning in concussion prediction and suggest its promise for future applications in biomechanical investigations of traumatic brain injury. PMID:29795640

Concussion classification via deep learning using whole-brain white matter fiber strains.

PubMed

Cai, Yunliang; Wu, Shaoju; Zhao, Wei; Li, Zhigang; Wu, Zheyang; Ji, Songbai

2018-01-01

Developing an accurate and reliable injury predictor is central to the biomechanical studies of traumatic brain injury. State-of-the-art efforts continue to rely on empirical, scalar metrics based on kinematics or model-estimated tissue responses explicitly pre-defined in a specific brain region of interest. They could suffer from loss of information. A single training dataset has also been used to evaluate performance but without cross-validation. In this study, we developed a deep learning approach for concussion classification using implicit features of the entire voxel-wise white matter fiber strains. Using reconstructed American National Football League (NFL) injury cases, leave-one-out cross-validation was employed to objectively compare injury prediction performances against two baseline machine learning classifiers (support vector machine (SVM) and random forest (RF)) and four scalar metrics via univariate logistic regression (Brain Injury Criterion (BrIC), cumulative strain damage measure of the whole brain (CSDM-WB) and the corpus callosum (CSDM-CC), and peak fiber strain in the CC). Feature-based machine learning classifiers including deep learning, SVM, and RF consistently outperformed all scalar injury metrics across all performance categories (e.g., leave-one-out accuracy of 0.828-0.862 vs. 0.690-0.776, and .632+ error of 0.148-0.176 vs. 0.207-0.292). Further, deep learning achieved the best cross-validation accuracy, sensitivity, AUC, and .632+ error. These findings demonstrate the superior performances of deep learning in concussion prediction and suggest its promise for future applications in biomechanical investigations of traumatic brain injury.

Novel Intrinsic Ignition Method Measuring Local-Global Integration Characterizes Wakefulness and Deep Sleep

PubMed Central

Tagliazucchi, Enzo; Sanjuán, Ana

2017-01-01

Abstract A precise definition of a brain state has proven elusive. Here, we introduce the novel local-global concept of intrinsic ignition characterizing the dynamical complexity of different brain states. Naturally occurring intrinsic ignition events reflect the capability of a given brain area to propagate neuronal activity to other regions, giving rise to different levels of integration. The ignitory capability of brain regions is computed by the elicited level of integration for each intrinsic ignition event in each brain region, averaged over all events. This intrinsic ignition method is shown to clearly distinguish human neuroimaging data of two fundamental brain states (wakefulness and deep sleep). Importantly, whole-brain computational modelling of this data shows that at the optimal working point is found where there is maximal variability of the intrinsic ignition across brain regions. Thus, combining whole brain models with intrinsic ignition can provide novel insights into underlying mechanisms of brain states. PMID:28966977

Novel Intrinsic Ignition Method Measuring Local-Global Integration Characterizes Wakefulness and Deep Sleep.

PubMed

Deco, Gustavo; Tagliazucchi, Enzo; Laufs, Helmut; Sanjuán, Ana; Kringelbach, Morten L

2017-01-01

A precise definition of a brain state has proven elusive. Here, we introduce the novel local-global concept of intrinsic ignition characterizing the dynamical complexity of different brain states. Naturally occurring intrinsic ignition events reflect the capability of a given brain area to propagate neuronal activity to other regions, giving rise to different levels of integration. The ignitory capability of brain regions is computed by the elicited level of integration for each intrinsic ignition event in each brain region, averaged over all events. This intrinsic ignition method is shown to clearly distinguish human neuroimaging data of two fundamental brain states (wakefulness and deep sleep). Importantly, whole-brain computational modelling of this data shows that at the optimal working point is found where there is maximal variability of the intrinsic ignition across brain regions. Thus, combining whole brain models with intrinsic ignition can provide novel insights into underlying mechanisms of brain states.

Atlas-Independent, Electrophysiological Mapping of the Optimal Locus of Subthalamic Deep Brain Stimulation for the Motor Symptoms of Parkinson Disease.

PubMed

Conrad, Erin C; Mossner, James M; Chou, Kelvin L; Patil, Parag G

2018-05-23

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease (PD). However, motor outcomes can be variable, perhaps due to inconsistent positioning of the active contact relative to an unknown optimal locus of stimulation. Here, we determine the optimal locus of STN stimulation in a geometrically unconstrained, mathematically precise, and atlas-independent manner, using Unified Parkinson Disease Rating Scale (UPDRS) motor outcomes and an electrophysiological neuronal stimulation model. In 20 patients with PD, we mapped motor improvement to active electrode location, relative to the individual, directly MRI-visualized STN. Our analysis included a novel, unconstrained and computational electrical-field model of neuronal activation to estimate the optimal locus of DBS. We mapped the optimal locus to a tightly defined ovoid region 0.49 mm lateral, 0.88 mm posterior, and 2.63 mm dorsal to the anatomical midpoint of the STN. On average, this locus is 11.75 lateral, 1.84 mm posterior, and 1.08 mm ventral to the mid-commissural point. Our novel, atlas-independent method reveals a single, ovoid optimal locus of stimulation in STN DBS for PD. The methodology, here applied to UPDRS and PD, is generalizable to atlas-independent mapping of other motor and non-motor effects of DBS. © 2018 S. Karger AG, Basel.

Evaluation of high-perimeter electrode designs for deep brain stimulation

NASA Astrophysics Data System (ADS)

Howell, Bryan; Grill, Warren M.

2014-08-01

Objective. Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, complications including infections and mis-programing following surgical replacement of the battery-powered implantable pulse generator adversely impact the safety profile of this therapy. We sought to decrease power consumption and extend battery life by modifying the electrode geometry to increase stimulation efficiency. The specific goal of this study was to determine whether electrode contact perimeter or area had a greater effect on increasing stimulation efficiency. Approach. Finite-element method (FEM) models of eight prototype electrode designs were used to calculate the electrode access resistance, and the FEM models were coupled with cable models of passing axons to quantify stimulation efficiency. We also measured in vitro the electrical properties of the prototype electrode designs and measured in vivo the stimulation efficiency following acute implantation in anesthetized cats. Main results. Area had a greater effect than perimeter on altering the electrode access resistance; electrode (access or dynamic) resistance alone did not predict stimulation efficiency because efficiency was dependent on the shape of the potential distribution in the tissue; and, quantitative assessment of stimulation efficiency required consideration of the effects of the electrode-tissue interface impedance. Significance. These results advance understanding of the features of electrode geometry that are important for designing the next generation of efficient DBS electrodes.

Low Frequency Stimulation Decreases Seizure Activity in a Mutation Model of Epilepsy

PubMed Central

Kile, Kara Buehrer; Tian, Nan; Durand, Dominique M.

2013-01-01

Summary Purpose To investigate brain electrical activity in Q54 mice that display spontaneous seizures because of a gain-of-function mutation of the Scn2a sodium channel gene, and to evaluate the efficacy of low frequency deep brain stimulation (DBS) for seizure frequency reduction. Methods EEG, EMG, and hippocampal deep electrodes were implanted into Q54 mice expressing an epileptic phenotype (n = 6). Chronic six channel recordings (wideband, 0.1–300 Hz) were stored 24 hours a day for more than 12 days. Low Frequency stimulation (LFS) (3Hz, square wave, biphasic, 100μs, 400μA) was applied to the ventral hippocampal commisure (VHC) in alternating five minute cycles (on or off) 24 hours a day for a period of four days. Results LFS (3Hz) resulted in a significant reduction in seizure frequency and duration (21% and 35%, p<0.05), when applied to the VHC of epileptic Q54 mice (n = 6). Seizure frequency was not directly affected by stimulation state (“on” versus “off”). Conclusion LFS applied at a frequency of 3Hz significantly reduced seizure frequency and duration in the Q54 model. Furthermore, the reduction of seizure frequency and duration by LFS was not immediate but had a delayed and lasting effect, supporting complex, indirect mechanisms of action. PMID:20659150

Brainstem stimulation increases functional connectivity of basal forebrain-paralimbic network in isoflurane-anesthetized rats.

PubMed

Pillay, Siveshigan; Liu, Xiping; Baracskay, Péter; Hudetz, Anthony G

2014-09-01

Brain states and cognitive-behavioral functions are precisely controlled by subcortical neuromodulatory networks. Manipulating key components of the ascending arousal system (AAS), via deep-brain stimulation, may help facilitate global arousal in anesthetized animals. Here we test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) under light isoflurane anesthesia, associated with loss of consciousness, leads to cortical desynchronization and specific changes in blood-oxygenation-level-dependent (BOLD) functional connectivity (FC) of the brain. BOLD signals were acquired simultaneously with frontal epidural electroencephalogram before and after PnO stimulation. Whole-brain FC was mapped using correlation analysis with seeds in major centers of the AAS. PnO stimulation produced cortical desynchronization, a decrease in δ- and θ-band power, and an increase in approximate entropy. Significant increases in FC after PnO stimulation occurred between the left nucleus Basalis of Meynert (NBM) as seed and numerous regions of the paralimbic network. Smaller increases in FC were present between the central medial thalamic nucleus and retrosplenium seeds and the left caudate putamen and NBM. The results suggest that, during light anesthesia, PnO stimulation preferentially modulates basal forebrain-paralimbic networks. We speculate that this may be a reflection of disconnected awareness.

New Directions in the Use of Brain Stimulation Interventions in Patients with Obsessive-Compulsive Disorder.

PubMed

Dell'Osso, Bernardo; Cremaschi, Laura; Oldani, Lucio; Altamura, Alfredo Carlo

2017-05-04

Obsessive-Compulsive Disorder (OCD) is a highly disabling condition with early onset and chronic course in most of the affected patients. In addition, OCD may show high comorbidity and suicide attempt rates, which worsen the overall burden of the disease for patients and their caregivers. First-line treatments for OCD consist of pro-serotonergic compounds and cognitive-behavioral therapy. Nonetheless, many patients show only limited benefit from such interventions and require additional "next-step" interventions, including augmentative antipsychotics and glutamate-modulating agents. Based on the knowledge about altered neurocircuitry in OCD, brain stimulation techniques, including transcranial magnetic and electrical stimulations (TMS and tDCS) and deep brain stimulation (DBS), have been increasingly investigated over the last decade, revealing positive results for otherwise intractable and treatment-refractory patients. Available evidence in the field is in continuous evolution and professionals actively involved in the management of OCD patients, psychiatrists in particular, need to be updated about latest developments. Through the analysis of controlled studies, meta-analyses and International treatment guidelines, the present article is aimed at providing the state of the art on the use of brain stimulation techniques for the treatment of OCD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Brain-machine interfaces: electrophysiological challenges and limitations.

PubMed

Lega, Bradley C; Serruya, Mijail D; Zaghloul, Kareem A

2011-01-01

Brain-machine interfaces (BMI) seek to directly communicate with the human nervous system in order to diagnose and treat intrinsic neurological disorders. While the first generation of these devices has realized significant clinical successes, they often rely on gross electrical stimulation using empirically derived parameters through open-loop mechanisms of action that are not yet fully understood. Their limitations reflect the inherent challenge in developing the next generation of these devices. This review identifies lessons learned from the first generation of BMI devices (chiefly deep brain stimulation), identifying key problems for which the solutions will aid the development of the next generation of technologies. Our analysis examines four hypotheses for the mechanism by which brain stimulation alters surrounding neurophysiologic activity. We then focus on motor prosthetics, describing various approaches to overcoming the problems of decoding neural signals. We next turn to visual prosthetics, an area for which the challenges of signal coding to match neural architecture has been partially overcome. Finally, we close with a review of cortical stimulation, examining basic principles that will be incorporated into the design of future devices. Throughout the review, we relate the issues of each specific topic to the common thread of BMI research: translating new knowledge of network neuroscience into improved devices for neuromodulation.

Processing-Induced Electrically Active Defects in Black Silicon Nanowire Devices.

PubMed

Carapezzi, Stefania; Castaldini, Antonio; Mancarella, Fulvio; Poggi, Antonella; Cavallini, Anna

2016-04-27

Silicon nanowires (Si NWs) are widely investigated nowadays for implementation in advanced energy conversion and storage devices, as well as many other possible applications. Black silicon (BSi)-NWs are dry etched NWs that merge the advantages related to low-dimensionality with the special industrial appeal connected to deep reactive ion etching (RIE). In fact, RIE is a well established technique in microelectronics manufacturing. However, RIE processing could affect the electrical properties of BSi-NWs by introducing deep states into their forbidden gap. This work applies deep level transient spectroscopy (DLTS) to identify electrically active deep levels and the associated defects in dry etched Si NW arrays. Besides, the successful fitting of DLTS spectra of BSi-NWs-based Schottky barrier diodes is an experimental confirmation that the same theoretical framework of dynamic electronic behavior of deep levels applies in bulk as well as in low dimensional structures like NWs, when quantum confinement conditions do not occur. This has been validated for deep levels associated with simple pointlike defects as well as for deep levels associated with defects with richer structures, whose dynamic electronic behavior implies a more complex picture.

Deep brain stimulation as a functional scalpel.

PubMed

Broggi, G; Franzini, A; Tringali, G; Ferroli, P; Marras, C; Romito, L; Maccagnano, E

2006-01-01

Since 1995, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan (INNCB,) 401 deep brain electrodes were implanted to treat several drug-resistant neurological syndromes (Fig. 1). More than 200 patients are still available for follow-up and therapeutical considerations. In this paper our experience is reviewed and pioneered fields are highlighted. The reported series of patients extends the use of deep brain stimulation beyond the field of Parkinson's disease to new fields such as cluster headache, disruptive behaviour, SUNCt, epilepsy and tardive dystonia. The low complication rate, the reversibility of the procedure and the available image guided surgery tools will further increase the therapeutic applications of DBS. New therapeutical applications are expected for this functional scalpel.

Deep brain stimulation of the internal pallidum in multiple system atrophy.

PubMed

Santens, Patrick; Patrick, Santens; Vonck, Kristl; Kristl, Vonck; De Letter, Miet; Miet, De Letter; Van Driessche, Katya; Katya, Van Driessche; Sieben, Anne; Anne, Sieben; De Reuck, Jacques; Jacques, De Reuck; Van Roost, Dirk; Dirk, Van Roost; Boon, Paul; Paul, Boon

2006-04-01

We describe the outcome of deep brain stimulation of the internal pallidum in a 57-year old patient with multiple system atrophy. Although the prominent dystonic features of this patient were markedly attenuated post-operatively, the outcome was to be considered unfavourable. There was a severe increase in akinesia resulting in overall decrease of mobility in limbs as well as in the face. As a result, the patient was anarthric and displayed dysphagia. A laterality effect of stimulation on oro-facial movements was demonstrated. The patient died 7 months post-operatively. This report adds to the growing consensus that multiple system atrophy patients are unsuitable candidates for deep brain stimulation.

Chinese expert consensus on programming deep brain stimulation for patients with Parkinson's disease.

PubMed

Chen, Shengdi; Gao, Guodong; Feng, Tao; Zhang, Jianguo

2018-01-01

Deep Brain Stimulation (DBS) therapy for the treatment of Parkinson's Disease (PD) is now a well-established option for some patients. Postoperative standardized programming processes can improve the level of postoperative management and programming, relieve symptoms and improve quality of life. In order to improve the quality of the programming, the experts on DBS and PD in neurology and neurosurgery in China reviewed the relevant literatures and combined their own experiences and developed this expert consensus on the programming of deep brain stimulation in patients with PD in China. This Chinese expert consensus on postoperative programming can standardize and improve postoperative management and programming of DBS for PD.

Analysis of evoked deep brain connectivity.

PubMed

Klimeš, Petr; Janeček, Jiři; Jurák, Pavel; Halámek, Josef; Chládek, Han; Brázdil, Milan

2013-01-01

Establishing dependencies and connectivity among different structures in the human brain is an extremely complex issue. Methods that are often used for connectivity analysis are based on correlation mechanisms. Correlation methods can analyze changes in signal shape or instantaneous power level. Although recent studies imply that observation of results from both groups of methods together can disclose some of the basic functions and behavior of the human brain during mental activity and decision-making, there is no technique covering changes in the shape of signals along with changes in their power levels. We present a method using a time evaluation of the correlation along with a comparison of power levels in every available contact pair from intracranial electrodes placed in deep brain structures. Observing shape changes in signals after stimulation together with their power levels provides us with new information about signal character between different structures in the brain during task-related events - visual stimulation with motor response. The results for a subject with 95 intracerebral contacts used in this paper demonstrate a clear methodology capable of spatially analyzing connectivity among deep brain structures.

Focal epidural cooling reduces the infarction volume of permanent middle cerebral artery occlusion in swine.

PubMed

Zhang, Lihua; Cheng, Huilin; Shi, Jixin; Chen, Jun

2007-02-01

The protective effect against ischemic stroke by systemic hypothermia is limited by the cooling rate and it has severe complications. This study was designed to evaluate the effect of SBH induced by epidural cooling on infarction volume in a swine model of PMCAO. Permanent middle cerebral artery occlusion was performed in 12 domestic swine assigned to groups A and B. In group A, the cranial and rectal temperatures were maintained at normal range (37 degrees C-39 degrees C) for 6 hours after PMCAO. In group B, cranial temperature was reduced to moderate (deep brain, <30 degrees C) and deep (brain surface, <20 degrees C) temperature and maintained at that level for 5 hours after 1 hour after PMCAO, by the epidural cooling method. All animals were euthanized 6 hours after MCAO; their brains were sectioned and stained with 2,3,5-triphenyltetrazolium chloride and their infarct volumes were calculated. The moderate and deep brain temperature (at deep brain and brain surface) can be induced by rapid epidural cooling, whereas the rectal temperature was maintained within normal range. The infarction volume after PMCAO was significantly reduced by epidural cooling compared with controls (13.73% +/- 1.82% vs 5.62% +/- 2.57%, P < .05). The present study has demonstrated, with histologic confirmation, that epidural cooling may be a useful strategy for reducing infarct volume after the onset of ischemia.

Closed loop deep brain stimulation: an evolving technology.

PubMed

Hosain, Md Kamal; Kouzani, Abbas; Tye, Susannah

2014-12-01

Deep brain stimulation is an effective and safe medical treatment for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, and treatment resistant obsessive compulsive disorder. A closed loop deep brain stimulation (CLDBS) system automatically adjusts stimulation parameters by the brain response in real time. The CLDBS continues to evolve due to the advancement in the brain stimulation technologies. This paper provides a study on the existing systems developed for CLDBS. It highlights the issues associated with CLDBS systems including feedback signal recording and processing, stimulation parameters setting, control algorithm, wireless telemetry, size, and power consumption. The benefits and limitations of the existing CLDBS systems are also presented. Whilst robust clinical proof of the benefits of the technology remains to be achieved, it has the potential to offer several advantages over open loop DBS. The CLDBS can improve efficiency and efficacy of therapy, eliminate lengthy start-up period for programming and adjustment, provide a personalized treatment, and make parameters setting automatic and adaptive.

Improvement of both dystonia and tics with 60 Hz pallidal deep brain stimulation.

PubMed

Hwynn, Nelson; Tagliati, Michele; Alterman, Ron L; Limotai, Natlada; Zeilman, Pamela; Malaty, Irene A; Foote, Kelly D; Morishita, Takashi; Okun, Michael S

2012-09-01

Deep brain stimulation has been utilized in both dystonia and in medication refractory Tourette syndrome. We present an interesting case of a patient with a mixture of disabling dystonia and Tourette syndrome whose coexistent dystonia and tics were successfully treated with 60 Hz-stimulation of the globus pallidus region.

Two-step tunneling technique of deep brain stimulation extension wires-a description.

PubMed

Fontaine, Denys; Vandersteen, Clair; Saleh, Christian; von Langsdorff, Daniel; Poissonnet, Gilles

2013-12-01

While a significant body of literature exists on the intracranial part of deep brain stimulation surgery, the equally important second part of the intervention related to the subcutaneous tunneling of deep brain stimulation extension wires is rarely described. The tunneling strategy can consist of a single passage of the extension wires from the frontal incision site to the subclavicular area, or of a two-step approach that adds a retro-auricular counter-incision. Each technique harbors the risk of intraoperative and postoperative complications. At our center, we perform a two-step tunneling procedure that we developed based on a cadaveric study. In 125 consecutive patients operated since 2002, we did not encounter any complication related to our tunneling method. Insufficient data exist to fully evaluate the advantages and disadvantages of each tunneling technique. It is of critical importance that authors detail their tunneling modus operandi and report the presence or absence of complications. This gathered data pool may help to formulate a definitive conclusions on the safest method for subcutaneous tunneling of extension wires in deep brain stimulation.

Synaptic Effects of Electric Fields

NASA Astrophysics Data System (ADS)

Rahman, Asif

Learning and sensory processing in the brain relies on the effective transmission of information across synapses. The strength and efficacy of synaptic transmission is modifiable through training and can be modulated with noninvasive electrical brain stimulation. Transcranial electrical stimulation (TES), specifically, induces weak intensity and spatially diffuse electric fields in the brain. Despite being weak, electric fields modulate spiking probability and the efficacy of synaptic transmission. These effects critically depend on the direction of the electric field relative to the orientation of the neuron and on the level of endogenous synaptic activity. TES has been used to modulate a wide range of neuropsychiatric indications, for various rehabilitation applications, and cognitive performance in diverse tasks. How can a weak and diffuse electric field, which simultaneously polarizes neurons across the brain, have precise changes in brain function? Designing therapies to maximize desired outcomes and minimize undesired effects presents a challenging problem. A series of experiments and computational models are used to define the anatomical and functional factors leading to specificity of TES. Anatomical specificity derives from guiding current to targeted brain structures and taking advantage of the direction-sensitivity of neurons with respect to the electric field. Functional specificity originates from preferential modulation of neuronal networks that are already active. Diffuse electric fields may recruit connected brain networks involved in a training task and promote plasticity along active synaptic pathways. In vitro, electric fields boost endogenous synaptic plasticity and raise the ceiling for synaptic learning with repeated stimulation sessions. Synapses undergoing strong plasticity are preferentially modulated over weak synapses. Therefore, active circuits that are involved in a task could be more susceptible to stimulation than inactive circuits. Moreover, stimulation polarity has asymmetric effects on synaptic strength making it easier to enhance ongoing plasticity. These results suggest that the susceptibility of brain networks to an electric field depends on the state of synaptic activity. Combining a training task, which activates specific circuits, with TES may lead to functionally-specific effects. Given the simplicity of TES and the complexity of brain function, understanding the mechanisms leading to specificity is fundamental to the rational advancement of TES.

An investigation into the induced electric fields from transcranial magnetic stimulation

NASA Astrophysics Data System (ADS)

Hadimani, Ravi; Lee, Erik; Duffy, Walter; Waris, Mohammed; Siddiqui, Waquar; Islam, Faisal; Rajamani, Mahesh; Nathan, Ryan; Jiles, David; David C Jiles Team; Walter Duffy Collaboration

Transcranial magnetic stimulation (TMS) is a promising tool for noninvasive brain stimulation that has been approved by the FDA for the treatment of major depressive disorder. To stimulate the brain, TMS uses large, transient pulses of magnetic field to induce an electric field in the head. This transient magnetic field is large enough to cause the depolarization of cortical neurons and initiate a synaptic signal transmission. For this study, 50 unique head models were created from MRI images. Previous simulation studies have primarily used a single head model, and thus give a limited image of the induced electric field from TMS. This study uses finite element analysis simulations on 50 unique, heterogeneous head models to better investigate the relationship between TMS and the electric field induced in brain tissues. Results showed a significant variation in the strength of the induced electric field in the brain, which can be reasonably predicted by the distance from the TMS coil to the stimulated brain. Further, it was seen that some models had high electric field intensities in over five times as much brain volume as other models.

Comparison of effectiveness between cork-screw and peg-screw electrodes for transcranial motor evoked potential monitoring using the finite element method.

PubMed

Tomio, Ryosuke; Akiyama, Takenori; Ohira, Takayuki; Yoshida, Kazunari

2016-01-01

Intraoperative monitoring of motor evoked potentials by transcranial electric stimulation is popular in neurosurgery for monitoring motor function preservation. Some authors have reported that the peg-screw electrodes screwed into the skull can more effectively conduct current to the brain compared to subdermal cork-screw electrodes screwed into the skin. The aim of this study was to investigate the influence of electrode design on transcranial motor evoked potential monitoring. We estimated differences in effectiveness between the cork-screw electrode, peg-screw electrode, and cortical electrode to produce electric fields in the brain. We used the finite element method to visualize electric fields in the brain generated by transcranial electric stimulation using realistic three-dimensional head models developed from T1-weighted images. Surfaces from five layers of the head were separated as accurately as possible. We created the "cork-screws model," "1 peg-screw model," "peg-screws model," and "cortical electrode model". Electric fields in the brain radially diffused from the brain surface at a maximum just below the electrodes in coronal sections. The coronal sections and surface views of the brain showed higher electric field distributions under the peg-screw compared to the cork-screw. An extremely high electric field was observed under cortical electrodes. Our main finding was that the intensity of electric fields in the brain are higher in the peg-screw model than the cork-screw model.

The inverse problem in electroencephalography using the bidomain model of electrical activity.

PubMed

Lopez Rincon, Alejandro; Shimoda, Shingo

2016-12-01

Acquiring information about the distribution of electrical sources in the brain from electroencephalography (EEG) data remains a significant challenge. An accurate solution would provide an understanding of the inner mechanisms of the electrical activity in the brain and information about damaged tissue. In this paper, we present a methodology for reconstructing brain electrical activity from EEG data by using the bidomain formulation. The bidomain model considers continuous active neural tissue coupled with a nonlinear cell model. Using this technique, we aim to find the brain sources that give rise to the scalp potential recorded by EEG measurements taking into account a non-static reconstruction. We simulate electrical sources in the brain volume and compare the reconstruction to the minimum norm estimates (MNEs) and low resolution electrical tomography (LORETA) results. Then, with the EEG dataset from the EEG Motor Movement/Imagery Database of the Physiobank, we identify the reaction to visual stimuli by calculating the time between stimulus presentation and the spike in electrical activity. Finally, we compare the activation in the brain with the registered activation using the LinkRbrain platform. Our methodology shows an improved reconstruction of the electrical activity and source localization in comparison with MNE and LORETA. For the Motor Movement/Imagery Database, the reconstruction is consistent with the expected position and time delay generated by the stimuli. Thus, this methodology is a suitable option for continuously reconstructing brain potentials. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Fos expression in the rat brain and spinal cord evoked by noxious stimulation to low back muscle and skin.

PubMed

Ohtori, S; Takahashi, K; Chiba, T; Takahashi, Y; Yamagata, M; Sameda, H; Moriya, H

2000-10-01

Acute noxious stimulation delivered to lumbar muscles and skin of rats was used to study Fos expression patterns in the brain and spinal cord. The present study was conducted to determine the differences in Fos expression in the brain and spinal cord as evoked by stimuli delivered to lumbar muscles and skin in rats. Patients with low back pain sometimes show psychological symptoms, such as quiescence, loss of interest, decreased activities, appetite loss, and restlessness. The pathway of deep somatic pain to the brain has been reported to be different from that of cutaneous pain. However, Fos expression has not been studied in the central nervous systems after stimulation of low back muscles. Rats were injected with 100 L of 5% formalin into the multifidus muscle (deep pain group; n = 10) and into the back skin of the L5 dermatome (cutaneous pain group; n = 10). Two hours after injection, the distribution of Fos-immunoreactive neurons was studied in the brain and spinal cord. Fos-immunoreactive neurons were observed in laminae I-V in the spinal cord in the cutaneous pain group, but they were not seen in lamina II in the deep pain group. In the brain, Fos-immunoreactive neurons were significantly more numerous in the deep pain group than in the cutaneous pain group in the piriform cortex, the accumbens nucleus core, the basolateral nucleus of amygdala, the paraventricular hypothalamic nucleus, the ventral tegmental area, and the ventrolateral periaqueductal gray. The finding that Fos-immunoreactive neurons were absent from lamina II of the spinal cord in the deep pain group is similar to that of the projection pattern of the visceral pain pathway. Fos expression in the ventrolateral periaqueductal gray in the deep pain group may represent a reaction of quiescence and a loss of interest, activities, or appetite. Furthermore, the detection of large numbers of Fos-immunoreactive neurons in the core of accumbens nucleus, basolateral nucleus of amygdala, paraventricular hypothalamic nucleus, and ventral tegmental area in the deep pain group may suggest a dominant reaction of dopaminergic neurons to stress, and a different information processing pathway than from that of cutaneous pain.

The clinical outcomes of deep gray matter injury in children with cerebral palsy in relation with brain magnetic resonance imaging.

PubMed

Choi, Ja Young; Choi, Yoon Seong; Rha, Dong-Wook; Park, Eun Sook

2016-08-01

In the present study we investigated the nature and extent of clinical outcomes using various classifications and analyzed the relationship between brain magnetic resonance imaging (MRI) findings and the extent of clinical outcomes in children with cerebral palsy (CP) with deep gray matter injury. The deep gray matter injuries of 69 children were classified into hypoxic ischemic encephalopathy (HIE) and kernicterus patterns. HIE patterns were divided into four groups (I-IV) based on severity. Functional classification was investigated using the gross motor function classification system-expanded and revised, manual ability classification system, communication function classification system, and tests of cognitive function, and other associated problems. The severity of HIE pattern on brain MRI was strongly correlated with the severity of clinical outcomes in these various domains. Children with a kernicterus pattern showed a wide range of clinical outcomes in these areas. Children with severe HIE are at high risk of intellectual disability (ID) or epilepsy and children with a kernicterus pattern are at risk of hearing impairment and/or ID. Grading severity of HIE pattern on brain MRI is useful for predicting overall outcomes. The clinical outcomes of children with a kernicterus pattern range widely from mild to severe. Delineation of the clinical outcomes of children with deep gray matter injury, which are a common abnormal brain MRI finding in children with CP, is necessary. The present study provides clinical outcomes for various domains in children with deep gray matter injury on brain MRI. The deep gray matter injuries were divided into two major groups; HIE and kernicterus patterns. Our study showed that severity of HIE pattern on brain MRI was strongly associated with the severity of impairments in gross motor function, manual ability, communication function, and cognition. These findings suggest that severity of HIE pattern can be useful for predicting the severity of impairments. Conversely, children with a kernicterus pattern showed a wide range of clinical outcomes in various domains. Children with severe HIE pattern are at high risk of ID or epilepsy and children with kernicterus pattern are at risk of hearing impairment or ID. The strength of our study was the assessment of clinical outcomes after 3 years of age using standardized classification systems in various domains in children with deep gray matter injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuronal inhibition and synaptic plasticity of basal ganglia neurons in Parkinson's disease

PubMed Central

Milosevic, Luka; Kalia, Suneil K; Hodaie, Mojgan; Lozano, Andres M; Fasano, Alfonso; Popovic, Milos R; Hutchison, William D

2018-01-01

Abstract Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease symptoms. The therapeutic benefits of deep brain stimulation are frequency-dependent, but the underlying physiological mechanisms remain unclear. To advance deep brain stimulation therapy an understanding of fundamental mechanisms is critical. The objectives of this study were to (i) compare the frequency-dependent effects on cell firing in subthalamic nucleus and substantia nigra pars reticulata; (ii) quantify frequency-dependent effects on short-term plasticity in substantia nigra pars reticulata; and (iii) investigate effects of continuous long-train high frequency stimulation (comparable to conventional deep brain stimulation) on synaptic plasticity. Two closely spaced (600 µm) microelectrodes were advanced into the subthalamic nucleus (n = 27) and substantia nigra pars reticulata (n = 14) of 22 patients undergoing deep brain stimulation surgery for Parkinson’s disease. Cell firing and evoked field potentials were recorded with one microelectrode during stimulation trains from the adjacent microelectrode across a range of frequencies (1–100 Hz, 100 µA, 0.3 ms, 50–60 pulses). Subthalamic firing attenuated with ≥20 Hz (P < 0.01) stimulation (silenced at 100 Hz), while substantia nigra pars reticulata decreased with ≥3 Hz (P < 0.05) (silenced at 50 Hz). Substantia nigra pars reticulata also exhibited a more prominent increase in transient silent period following stimulation. Patients with longer silent periods after 100 Hz stimulation in the subthalamic nucleus tended to have better clinical outcome after deep brain stimulation. At ≥30 Hz the first evoked field potential of the stimulation train in substantia nigra pars reticulata was potentiated (P < 0.05); however, the average amplitude of the subsequent potentials was rapidly attenuated (P < 0.01). This is suggestive of synaptic facilitation followed by rapid depression. Paired pulse ratios calculated at the beginning of the train revealed that 20 Hz (P < 0.05) was the minimum frequency required to induce synaptic depression. Lastly, the average amplitude of evoked field potentials during 1 Hz pulses showed significant inhibitory synaptic potentiation after long-train high frequency stimulation (P < 0.001) and these increases were coupled with increased durations of neuronal inhibition (P < 0.01). The subthalamic nucleus exhibited a higher frequency threshold for stimulation-induced inhibition than the substantia nigra pars reticulata likely due to differing ratios of GABA:glutamate terminals on the soma and/or the nature of their GABAergic inputs (pallidal versus striatal). We suggest that enhancement of inhibitory synaptic plasticity, and frequency-dependent potentiation and depression are putative mechanisms of deep brain stimulation. Furthermore, we foresee that future closed-loop deep brain stimulation systems (with more frequent off stimulation periods) may benefit from inhibitory synaptic potentiation that occurs after high frequency stimulation. PMID:29236966

Using the brain's fight-or-flight response for predicting mental illness on the human space flight program

NASA Astrophysics Data System (ADS)

Losik, L.

A predictive medicine program allows disease and illness including mental illness to be predicted using tools created to identify the presence of accelerated aging (a.k.a. disease) in electrical and mechanical equipment. When illness and disease can be predicted, actions can be taken so that the illness and disease can be prevented and eliminated. A predictive medicine program uses the same tools and practices from a prognostic and health management program to process biological and engineering diagnostic data provided in analog telemetry during prelaunch readiness and space exploration missions. The biological and engineering diagnostic data necessary to predict illness and disease is collected from the pre-launch spaceflight readiness activities and during space flight for the ground crew to perform a prognostic analysis on the results from a diagnostic analysis. The diagnostic, biological data provided in telemetry is converted to prognostic (predictive) data using the predictive algorithms. Predictive algorithms demodulate telemetry behavior. They illustrate the presence of accelerated aging/disease in normal appearing systems that function normally. Mental illness can predicted using biological diagnostic measurements provided in CCSDS telemetry from a spacecraft such as the ISS or from a manned spacecraft in deep space. The measurements used to predict mental illness include biological and engineering data from an astronaut's circadian and ultranian rhythms. This data originates deep in the brain that is also damaged from the long-term exposure to cortisol and adrenaline anytime the body's fight or flight response is activated. This paper defines the brain's FOFR; the diagnostic, biological and engineering measurements needed to predict mental illness, identifies the predictive algorithms necessary to process the behavior in CCSDS analog telemetry to predict and thus prevent mental illness from occurring on human spaceflight missions.

Fiberless multicolor neural optoelectrode for in vivo circuit analysis.

PubMed

Kampasi, Komal; Stark, Eran; Seymour, John; Na, Kyounghwan; Winful, Herbert G; Buzsáki, György; Wise, Kensall D; Yoon, Euisik

2016-08-03

Maximizing the potential of optogenetic approaches in deep brain structures of intact animals requires optical manipulation of neurons at high spatial and temporal resolutions, while simultaneously recording electrical data from those neurons. Here, we present the first fiber-less optoelectrode with a monolithically integrated optical waveguide mixer that can deliver multicolor light at a common waveguide port to achieve multicolor modulation of the same neuronal population in vivo. We demonstrate successful device implementation by achieving efficient coupling between a side-emitting injection laser diode (ILD) and a dielectric optical waveguide mixer via a gradient-index (GRIN) lens. The use of GRIN lenses attains several design features, including high optical coupling and thermal isolation between ILDs and waveguides. We validated the packaged devices in the intact brain of anesthetized mice co-expressing Channelrhodopsin-2 and Archaerhodopsin in pyramidal cells in the hippocampal CA1 region, achieving high quality recording, activation and silencing of the exact same neurons in a given local region. This fully-integrated approach demonstrates the spatial precision and scalability needed to enable independent activation and silencing of the same or different groups of neurons in dense brain regions while simultaneously recording from them, thus considerably advancing the capabilities of currently available optogenetic toolsets.

Induction of panic attack by stimulation of the ventromedial hypothalamus.

PubMed

Wilent, W Bryan; Oh, Michael Y; Buetefisch, Cathrin M; Bailes, Julian E; Cantella, Diane; Angle, Cindy; Whiting, Donald M

2010-06-01

Panic attacks are sudden debilitating attacks of intense distress often accompanied by physical symptoms such as shortness of breath and heart palpitations. Numerous brain regions, hormones, and neurotransmitter systems are putatively involved, but the etiology and neurocircuitry of panic attacks is far from established. One particular brain region of interest is the ventromedial hypothalamus (VMH). In cats and rats, electrical stimulation delivered to the VMH has been shown to evoke an emotional "panic attack-like" escape behavior, and in humans, stimulation targeting nuclei just posterior or anterior to the VMH has reportedly induced panic attacks. The authors report findings obtained in an awake patient undergoing bilateral implantation of deep brain stimulation electrodes into the hypothalamus that strongly implicates the VMH as being critically involved in the genesis of panic attacks. First, as the stimulating electrode progressed deeper into the VMH, the intensity of stimulation required to evoke an attack systematically decreased; second, while stimulation of the VMH in either hemisphere evoked panic, stimulation that appeared to be in the center of the VMH was more potent. Thus, this evidence supports the role of the VMH in the induction of panic attacks purported by animal studies.

The phenomenology of deep brain stimulation-induced changes in OCD: an enactive affordance-based model

PubMed Central

de Haan, Sanneke; Rietveld, Erik; Stokhof, Martin; Denys, Damiaan

2013-01-01

People suffering from Obsessive-Compulsive Disorder (OCD) do things they do not want to do, and/or they think things they do not want to think. In about 10% of OCD patients, none of the available treatment options is effective. A small group of these patients is currently being treated with deep brain stimulation (DBS). DBS involves the implantation of electrodes in the brain. These electrodes give a continuous electrical pulse to the brain area in which they are implanted. It turns out that patients may experience profound changes as a result of DBS treatment. It is not just the symptoms that change; patients rather seem to experience a different way of being in the world. These global effects are insufficiently captured by traditional psychiatric scales, which mainly consist of behavioral measures of the severity of the symptoms. In this article we aim to capture the changes in the patients' phenomenology and make sense of the broad range of changes they report. For that we introduce an enactive, affordance-based model that fleshes out the dynamic interactions between person and world in four aspects. The first aspect is the patients' experience of the world. We propose to specify the patients' world in terms of a field of affordances, with the three dimensions of broadness of scope (“width” of the field), temporal horizon (“depth”), and relevance of the perceived affordances (“height”). The second aspect is the person-side of the interaction, that is, the patients' self-experience, notably their moods and feelings. Thirdly, we point to the different characteristics of the way in which patients relate to the world. And lastly, the existential stance refers to the stance that patients take toward the changes they experience: the second-order evaluative relation to their interactions and themselves. With our model we intend to specify the notion of being in the world in order to do justice to the phenomenological effects of DBS treatment. PMID:24133438

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization.

PubMed

Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P; Johnson, G Allan

2015-08-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. © 2015 Wiley Periodicals, Inc.

Recording evoked potentials during deep brain stimulation: development and validation of instrumentation to suppress the stimulus artefact.

PubMed

Kent, A R; Grill, W M

2012-06-01

The clinical efficacy of deep brain stimulation (DBS) for the treatment of movement disorders depends on the identification of appropriate stimulation parameters. Since the mechanisms of action of DBS remain unclear, programming sessions can be time consuming, costly and result in sub-optimal outcomes. Measurement of electrically evoked compound action potentials (ECAPs) during DBS, generated by activated neurons in the vicinity of the stimulating electrode, could offer insight into the type and spatial extent of neural element activation and provide a potential feedback signal for the rational selection of stimulation parameters and closed-loop DBS. However, recording ECAPs presents a significant technical challenge due to the large stimulus artefact, which can saturate recording amplifiers and distort short latency ECAP signals. We developed DBS-ECAP recording instrumentation combining commercial amplifiers and circuit elements in a serial configuration to reduce the stimulus artefact and enable high fidelity recording. We used an electrical circuit equivalent model of the instrumentation to understand better the sources of the stimulus artefact and the mechanisms of artefact reduction by the circuit elements. In vitro testing validated the capability of the instrumentation to suppress the stimulus artefact and increase gain by a factor of 1000 to 5000 compared to a conventional biopotential amplifier. The distortion of mock ECAP (mECAP) signals was measured across stimulation parameters, and the instrumentation enabled high fidelity recording of mECAPs with latencies of only 0.5 ms for DBS pulse widths of 50 to 100 µs/phase. Subsequently, the instrumentation was used to record in vivo ECAPs, without contamination by the stimulus artefact, during thalamic DBS in an anesthetized cat. The characteristics of the physiological ECAP were dependent on stimulation parameters. The novel instrumentation enables high fidelity ECAP recording and advances the potential use of the ECAP as a feedback signal for the tuning of DBS parameters.

Apparent isotropic electrical property for electrical brain stimulation (EBS) using magnetic resonance diffusion weighted imaging (MR-DWI)

NASA Astrophysics Data System (ADS)

Lee, Mun Bae; Kwon, Oh-In

2018-04-01

Electrical brain stimulation (EBS) is an invasive electrotherapy and technique used in brain neurological disorders through direct or indirect stimulation using a small electric current. EBS has relied on computational modeling to achieve optimal stimulation effects and investigate the internal activations. Magnetic resonance diffusion weighted imaging (DWI) is commonly useful for diagnosis and investigation of tissue functions in various organs. The apparent diffusion coefficient (ADC) measures the intensity of water diffusion within biological tissues using DWI. By measuring trace ADC and magnetic flux density induced by the EBS, we propose a method to extract electrical properties including the effective extracellular ion-concentration (EEIC) and the apparent isotropic conductivity without any auxiliary additional current injection. First, the internal current density due to EBS is recovered using the measured one component of magnetic flux density. We update the EEIC by introducing a repetitive scheme called the diffusion weighting J-substitution algorithm using the recovered current density and the trace ADC. To verify the proposed method, we study an anesthetized canine brain to visualize electrical properties including electrical current density, effective extracellular ion-concentration, and effective isotropic conductivity by applying electrical stimulation of the brain.

Brain tumor classification of microscopy images using deep residual learning

NASA Astrophysics Data System (ADS)

Ishikawa, Yota; Washiya, Kiyotada; Aoki, Kota; Nagahashi, Hiroshi

2016-12-01

The crisis rate of brain tumor is about one point four in ten thousands. In general, cytotechnologists take charge of cytologic diagnosis. However, the number of cytotechnologists who can diagnose brain tumors is not sufficient, because of the necessity of highly specialized skill. Computer-Aided Diagnosis by computational image analysis may dissolve the shortage of experts and support objective pathological examinations. Our purpose is to support a diagnosis from a microscopy image of brain cortex and to identify brain tumor by medical image processing. In this study, we analyze Astrocytes that is a type of glia cell of central nerve system. It is not easy for an expert to discriminate brain tumor correctly since the difference between astrocytes and low grade astrocytoma (tumors formed from Astrocyte) is very slight. In this study, we present a novel method to segment cell regions robustly using BING objectness estimation and to classify brain tumors using deep convolutional neural networks (CNNs) constructed by deep residual learning. BING is a fast object detection method and we use pretrained BING model to detect brain cells. After that, we apply a sequence of post-processing like Voronoi diagram, binarization, watershed transform to obtain fine segmentation. For classification using CNNs, a usual way of data argumentation is applied to brain cells database. Experimental results showed 98.5% accuracy of classification and 98.2% accuracy of segmentation.

Perturbation and Nonlinear Dynamic Analysis of Acoustic Phonatory Signal in Parkinsonian Patients Receiving Deep Brain Stimulation

ERIC Educational Resources Information Center

Lee, Victoria S.; Zhou, Xiao Ping; Rahn, Douglas A., III; Wang, Emily Q.; Jiang, Jack J.

2008-01-01

Nineteen PD patients who received deep brain stimulation (DBS), 10 non-surgical (control) PD patients, and 11 non-pathologic age- and gender-matched subjects performed sustained vowel phonations. The following acoustic measures were obtained on the sustained vowel phonations: correlation dimension (D[subscript 2]), percent jitter, percent shimmer,…

Practical considerations and nuances in anesthesia for patients undergoing deep brain stimulation implantation surgery.

PubMed

Scharpf, Danielle Teresa; Sharma, Mayur; Deogaonkar, Milind; Rezai, Ali; Bergese, Sergio D

2015-08-01

The field of functional neurosurgery has expanded in last decade to include newer indications, new devices, and new methods. This advancement has challenged anesthesia providers to adapt to these new requirements. This review aims to discuss the nuances and practical issues that are faced while administering anesthesia for deep brain stimulation surgery.

Designing a deep brain stimulator to suppress pathological neuronal synchrony.

PubMed

Montaseri, Ghazal; Yazdanpanah, Mohammad Javad; Bahrami, Fariba

2015-03-01

Some of neuropathologies are believed to be related to abnormal synchronization of neurons. In the line of therapy, designing effective deep brain stimulators to suppress the pathological synchrony among neuronal ensembles is a challenge of high clinical relevance. The stimulation should be able to disrupt the synchrony in the presence of latencies due to imperfect knowledge about parameters of a neuronal ensemble and stimulation impacts on the ensemble. We propose an adaptive desynchronizing deep brain stimulator capable of dealing with these uncertainties. We analyze the collective behavior of the stimulated neuronal ensemble and show that, using the designed stimulator, the resulting asynchronous state is stable. Simulation results reveal the efficiency of the proposed technique. Copyright © 2014 Elsevier Ltd. All rights reserved.

Electric Field Encephalography as a tool for functional brain research: a modeling study.

PubMed

Petrov, Yury; Sridhar, Srinivas

2013-01-01

We introduce the notion of Electric Field Encephalography (EFEG) based on measuring electric fields of the brain and demonstrate, using computer modeling, that given the appropriate electric field sensors this technique may have significant advantages over the current EEG technique. Unlike EEG, EFEG can be used to measure brain activity in a contactless and reference-free manner at significant distances from the head surface. Principal component analysis using simulated cortical sources demonstrated that electric field sensors positioned 3 cm away from the scalp and characterized by the same signal-to-noise ratio as EEG sensors provided the same number of uncorrelated signals as scalp EEG. When positioned on the scalp, EFEG sensors provided 2-3 times more uncorrelated signals. This significant increase in the number of uncorrelated signals can be used for more accurate assessment of brain states for non-invasive brain-computer interfaces and neurofeedback applications. It also may lead to major improvements in source localization precision. Source localization simulations for the spherical and Boundary Element Method (BEM) head models demonstrated that the localization errors are reduced two-fold when using electric fields instead of electric potentials. We have identified several techniques that could be adapted for the measurement of the electric field vector required for EFEG and anticipate that this study will stimulate new experimental approaches to utilize this new tool for functional brain research.

Assessing the temporal stability of spatial patterns of soil apparent electrical conductivity using geophysical methods

NASA Astrophysics Data System (ADS)

De Caires, Sunshine A.; Wuddivira, Mark N.; Bekele, Isaac

2014-10-01

Cocoa remains in the same field for decades, resulting in plantations dominated with aging trees growing on variable and depleted soils. We determined the spatio-temporal variability of key soil properties in a (5.81 ha) field from the International Cocoa Genebank, Trinidad using geophysical methods. Multi-year (2008-2009) measurements of apparent electrical conductivity at 0-0.75 m (shallow) and 0.75-1.5 m (deep) were conducted. Apparent electrical conductivity at deep and shallow gave the strongest linear correlation with clay-silt content (R = 0.67 and R = 0.78, respectively) and soil solution electrical conductivity (R = 0.76 and R = 0.60, respectively). Spearman rank correlation coefficients ranged between 0.89-0.97 and 0.81- 0.95 for apparent electrical conductivity at deep and shallow, respectively, signifying a strong linear dependence between measurement days. Thus, in the humid tropics, cocoa fields with thick organic litter layer and relatively dense understory cover, experience minimal fluctuations in transient properties of soil water and temperature at the topsoil resulting in similarly stable apparent electrical conductivity at shallow and deep. Therefore, apparent electrical conductivity at shallow, which covers the depth where cocoa feeder roots concentrate, can be used as a fertility indicator and to develop soil zones for efficient application of inputs and management of cocoa fields.

76 FR 48062 - Effective Date of Requirement for Premarket Approval for Cranial Electrotherapy Stimulator

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-08

... devices include headaches following treatment with electrical stimulation. Potential risk of seizure--electrical stimulation of the brain may result in seizures, particularly in patients with a history of... effects from electrical stimulation of the brain--The physiological effects associated with electrical...

Offshore Floating Wind Turbine-driven Deep Sea Water Pumping for Combined Electrical Power and District Cooling

NASA Astrophysics Data System (ADS)

Sant, T.; Buhagiar, D.; Farrugia, R. N.

2014-06-01

A new concept utilising floating wind turbines to exploit the low temperatures of deep sea water for space cooling in buildings is presented. The approach is based on offshore hydraulic wind turbines pumping pressurised deep sea water to a centralised plant consisting of a hydro-electric power system coupled to a large-scale sea water-cooled air conditioning (AC) unit of an urban district cooling network. In order to investigate the potential advantages of this new concept over conventional technologies, a simplified model for performance simulation of a vapour compression AC unit was applied independently to three different systems, with the AC unit operating with (1) a constant flow of sea surface water, (2) a constant flow of sea water consisting of a mixture of surface sea water and deep sea water delivered by a single offshore hydraulic wind turbine and (3) an intermittent flow of deep sea water pumped by a single offshore hydraulic wind turbine. The analysis was based on one year of wind and ambient temperature data for the Central Mediterranean that is known for its deep waters, warm climate and relatively low wind speeds. The study confirmed that while the present concept is less efficient than conventional turbines utilising grid-connected electrical generators, a significant portion of the losses associated with the hydraulic transmission through the pipeline are offset by the extraction of cool deep sea water which reduces the electricity consumption of urban air-conditioning units.

Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation

PubMed Central

Huang, Yu; Liu, Anli A; Lafon, Belen; Friedman, Daniel; Dayan, Michael; Wang, Xiuyuan; Bikson, Marom; Doyle, Werner K; Devinsky, Orrin; Parra, Lucas C

2017-01-01

Transcranial electric stimulation aims to stimulate the brain by applying weak electrical currents at the scalp. However, the magnitude and spatial distribution of electric fields in the human brain are unknown. We measured electric potentials intracranially in ten epilepsy patients and estimated electric fields across the entire brain by leveraging calibrated current-flow models. When stimulating at 2 mA, cortical electric fields reach 0.8 V/m, the lower limit of effectiveness in animal studies. When individual whole-head anatomy is considered, the predicted electric field magnitudes correlate with the recorded values in cortical (r = 0.86) and depth (r = 0.88) electrodes. Accurate models require adjustment of tissue conductivity values reported in the literature, but accuracy is not improved when incorporating white matter anisotropy or different skull compartments. This is the first study to validate and calibrate current-flow models with in vivo intracranial recordings in humans, providing a solid foundation to target stimulation and interpret clinical trials. DOI: http://dx.doi.org/10.7554/eLife.18834.001 PMID:28169833

Deep-Learning Technique To Convert a Crude Piezoresistive Carbon Nanotube-Ecoflex Composite Sheet into a Smart, Portable, Disposable, and Extremely Flexible Keypad.

PubMed

Lee, Jin-Woong; Chung, Jiyong; Cho, Min-Young; Timilsina, Suman; Sohn, Keemin; Kim, Ji Sik; Sohn, Kee-Sun

2018-06-20

An extremely simple bulk sheet made of a piezoresistive carbon nanotube (CNT)-Ecoflex composite can act as a smart keypad that is portable, disposable, and flexible enough to be carried crushed inside the pocket of a pair of trousers. Both a rigid-button-imbedded, rollable (or foldable) pad and a patterned flexible pad have been introduced for use as portable keyboards. Herein, we suggest a bare, bulk, macroscale piezoresistive sheet as a replacement for these complex devices that are achievable only through high-cost fabrication processes such as patterning-based coating, printing, deposition, and mounting. A deep-learning technique based on deep neural networks (DNN) enables this extremely simple bulk sheet to play the role of a smart keypad without the use of complicated fabrication processes. To develop this keypad, instantaneous electrical resistance change was recorded at several locations on the edge of the sheet along with the exact information on the touch position and pressure for a huge number of random touches. The recorded data were used for training a DNN model that could eventually act as a brain for a simple sheet-type keypad. This simple sheet-type keypad worked perfectly and outperformed all of the existing portable keypads in terms of functionality, flexibility, disposability, and cost.

Conformable actively multiplexed high-density surface electrode array for brain interfacing

DOEpatents

Rogers, John; Kim, Dae-Hyeong; Litt, Brian; Viventi, Jonathan

2015-01-13

Provided are methods and devices for interfacing with brain tissue, specifically for monitoring and/or actuation of spatio-temporal electrical waveforms. The device is conformable having a high electrode density and high spatial and temporal resolution. A conformable substrate supports a conformable electronic circuit and a barrier layer. Electrodes are positioned to provide electrical contact with a brain tissue. A controller monitors or actuates the electrodes, thereby interfacing with the brain tissue. In an aspect, methods are provided to monitor or actuate spatio-temporal electrical waveform over large brain surface areas by any of the devices disclosed herein.

Deep learning for neuroimaging: a validation study.

PubMed

Plis, Sergey M; Hjelm, Devon R; Salakhutdinov, Ruslan; Allen, Elena A; Bockholt, Henry J; Long, Jeffrey D; Johnson, Hans J; Paulsen, Jane S; Turner, Jessica A; Calhoun, Vince D

2014-01-01

Deep learning methods have recently made notable advances in the tasks of classification and representation learning. These tasks are important for brain imaging and neuroscience discovery, making the methods attractive for porting to a neuroimager's toolbox. Success of these methods is, in part, explained by the flexibility of deep learning models. However, this flexibility makes the process of porting to new areas a difficult parameter optimization problem. In this work we demonstrate our results (and feasible parameter ranges) in application of deep learning methods to structural and functional brain imaging data. These methods include deep belief networks and their building block the restricted Boltzmann machine. We also describe a novel constraint-based approach to visualizing high dimensional data. We use it to analyze the effect of parameter choices on data transformations. Our results show that deep learning methods are able to learn physiologically important representations and detect latent relations in neuroimaging data.

Deep brain stimulation of the pedunculopontine nucleus for treatment of gait and balance disorder in progressive supranuclear palsy: Effects of frequency modulations and clinical outcome.

PubMed

Galazky, Imke; Kaufmann, Jörn; Lorenzl, Stefan; Ebersbach, Georg; Gandor, Florin; Zaehle, Tino; Specht, Sylke; Stallforth, Sabine; Sobieray, Uwe; Wirkus, Edyta; Casjens, Franziska; Heinze, Hans-Jochen; Kupsch, Andreas; Voges, Jürgen

2018-05-01

The pedunculopontine nucleus has been suggested as a potential deep brain stimulation target for axial symptoms such as gait and balance impairment in idiopathic Parkinson's disease as well as atypical Parkinsonian disorders. Seven consecutive patients with progressive supranuclear palsy received bilateral pedunculopontine nucleus deep brain stimulation. Inclusion criteria comprised of the clinical diagnosis of progressive supranuclear palsy, a levodopa-resistant gait and balance disorder, age <75 years, and absence of dementia or major psychiatric co-morbidities. Effects of stimulation frequencies at 8, 20, 60 and 130 Hz on motor scores and gait were assessed. Motor scores were followed up for two years postoperatively. Activities of daily living, frequency of falls, health-related quality of life, cognition and mood at 12 months were compared to baseline parameters. Surgical and stimulation related adverse events were assessed. Bilateral pedunculopontine nucleus deep brain stimulation at 8 Hz significantly improved axial motor symptoms and cyclic gait parameters, while high frequency stimulation did not ameliorate gait and balance but improved hypokinesia. This improvement however did not translate into clinically relevant benefits. Frequency of falls was not reduced. Activities of daily living, quality of life and frontal cognitive functions declined, while mood remained unchanged. Bilateral pedunculopontine nucleus deep brain stimulation in progressive supranuclear palsy generates frequency-dependent effects with improvement of cyclic gait parameters at low frequency and amelioration of hypokinesia at high frequency stimulation. However, these effects do not translate into a clinically important improvement. Copyright © 2018. Published by Elsevier Ltd.

The MDS-UPDRS tracks motor and non-motor improvement due to subthalamic nucleus deep brain stimulation in Parkinson disease.

PubMed

Chou, Kelvin L; Taylor, Jennifer L; Patil, Parag G

2013-11-01

The Movement Disorders Society revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) improves upon the original UPDRS by adding more non-motor items, making it a more robust tool to evaluate the severity of motor and non-motor symptoms of Parkinson disease. Previous studies on deep brain stimulation have not used the MDS-UPDRS. To determine if the MDS-UPDRS could detect improvement in both motor and non-motor symptoms after bilateral subthalamic nucleus deep brain stimulation for Parkinson disease. We compared scores on the entire MDS-UPDRS prior to surgery (baseline) and approximately six months following the initial programming visit in twenty subjects (12M/8F) with Parkinson disease undergoing bilateral subthalamic nucleus deep brain stimulation. STN DBS significantly improved the scores for every section of the MDS-UPDRS at the 6 month follow-up. Part I improved by 3.1 points (22%), Part II by 5.3 points (29%), Part III by 13.1 points (29%) with stimulation alone, and Part IV by 7.1 points (74%). Individual non-motor items in Part I that improved significantly were constipation, light-headedness, and fatigue. Both motor and non-motor symptoms, as assessed by the MDS-UPDRS, improve with bilateral subthalamic nucleus stimulation six months after the stimulator is turned on. We recommend that the MDS-UPDRS be utilized in future deep brain stimulation studies because of the advantage of detecting change in non-motor symptoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Resting state cortical oscillations of patients with Parkinson disease and with and without subthalamic deep brain stimulation: a magnetoencephalography study.

PubMed

Cao, Chunyan; Li, Dianyou; Jiang, Tianxiao; Ince, Nuri Firat; Zhan, Shikun; Zhang, Jing; Sha, Zhiyi; Sun, Bomin

2015-04-01

In this study, we investigate the modification to cortical oscillations of patients with Parkinson disease (PD) by subthalamic deep brain stimulation (STN-DBS). Spontaneous cortical oscillations of patients with PD were recorded with magnetoencephalography during on and off subthalamic nucleus deep brain stimulation states. Several features such as average frequency, average power, and relative subband power in regions of interest were extracted in the frequency domain, and these features were correlated with Unified Parkinson Disease Rating Scale III evaluation. The same features were also investigated in patients with PD without surgery and healthy controls. Patients with Parkinson disease without surgery compared with healthy controls had a significantly lower average frequency and an increased average power in 1 to 48 Hz range in whole cortex. Higher relative power in theta and simultaneous decrease in beta and gamma over temporal and occipital were also observed in patients with PD. The Unified Parkinson Disease Rating Scale III rigidity score correlated with the average frequency and with the relative power of beta and gamma in frontal areas. During subthalamic nucleus deep brain stimulation, the average frequency increased significantly when stimulation was on compared with off state. In addition, the relative power dropped in delta, whereas it rose in beta over the whole cortex. Through the course of stimulation, the Unified Parkinson Disease Rating Scale III rigidity and tremor scores correlated with the relative power of alpha over left parietal. Subthalamic nucleus deep brain stimulation improves the symptoms of PD by suppressing the synchronization of alpha rhythm in somatomotor region.

Deep-level dominated electrical characteristics of Au contacts on beta-SiC

NASA Technical Reports Server (NTRS)

Das, K.; Kong, H. S.; Petit, J. B.; Bumgarner, J. W.; Davis, R. F.; Matus, L. G.

1990-01-01

Electrical characteristics of Au contacts on beta-SiC films, grown epitaxially on both nominal and off-axis (100) silicon substrates, are reported. An analysis of the logarithmic I-V plots of the Au/beta-SiC diodes revealed information pertaining to the deep states present in the materials. It was found that while the beta-SiC films grown on nominally (100) oriented substrates show the presence of two deep levels located between 0.26 and 0.38 eV below the conduction bandedge, the beta-SiC films deposited on off-axis substrates have only one deep level, located about 0.49 eV below the conduction bandedge for the 2-deg off (100) substrates and 0.57 eV for the 4-deg off (100) substrates. The presence of the shallower deep states in the beta-SiC films grown on nominal (100) substrates is attributed to the electrical activity of antiphase domain boundaries.

Intensive Voice Treatment (LSVT[R]LOUD) for Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus

ERIC Educational Resources Information Center

Spielman, Jennifer; Mahler, Leslie; Halpern, Angela; Gilley, Phllip; Klepitskaya, Olga; Ramig, Lorraine

2011-01-01

Purpose: Intensive voice therapy (LSVT[R]LOUD) can effectively manage voice and speech symptoms associated with idiopathic Parkinson disease (PD). This small-group study evaluated voice and speech in individuals with and without deep brain stimulation of the subthalamic nucleus (STN-DBS) before and after LSVT LOUD, to determine whether outcomes…

Update on Deep Brain Stimulation for Dyskinesia and Dystonia: A Literature Review

PubMed Central

TODA, Hiroki; SAIKI, Hidemoto; NISHIDA, Namiko; IWASAKI, Koichi

2016-01-01

Deep brain stimulation (DBS) has been an established surgical treatment option for dyskinesia from Parkinson disease and for dystonia. The present article deals with the timing of surgical intervention, selecting an appropriate target, and minimizing adverse effects. We provide an overview of current evidences and issues for dyskinesia and dystonia as well as emerging DBS technology. PMID:27053331

Implementation of a smartphone wireless accelerometer platform for establishing deep brain stimulation treatment efficacy of essential tremor with machine learning.

PubMed

LeMoyne, Robert; Tomycz, Nestor; Mastroianni, Timothy; McCandless, Cyrus; Cozza, Michael; Peduto, David

2015-01-01

Essential tremor (ET) is a highly prevalent movement disorder. Patients with ET exhibit a complex progressive and disabling tremor, and medical management often fails. Deep brain stimulation (DBS) has been successfully applied to this disorder, however there has been no quantifiable way to measure tremor severity or treatment efficacy in this patient population. The quantified amelioration of kinetic tremor via DBS is herein demonstrated through the application of a smartphone (iPhone) as a wireless accelerometer platform. The recorded acceleration signal can be obtained at a setting of the subject's convenience and conveyed by wireless transmission through the Internet for post-processing anywhere in the world. Further post-processing of the acceleration signal can be classified through a machine learning application, such as the support vector machine. Preliminary application of deep brain stimulation with a smartphone for acquisition of a feature set and machine learning for classification has been successfully applied. The support vector machine achieved 100% classification between deep brain stimulation in `on' and `off' mode based on the recording of an accelerometer signal through a smartphone as a wireless accelerometer platform.

Unilateral pedunculopontine stimulation improves falls in Parkinson's disease.

PubMed

Moro, Elena; Hamani, Clement; Poon, Yu-Yan; Al-Khairallah, Thamar; Dostrovsky, Jonathan O; Hutchison, William D; Lozano, Andres M

2010-01-01

Postural instability and falls are a major source of disability in patients with advanced Parkinson's disease. These problems are currently not well addressed by either pharmacotherapy nor by subthalamic nucleus deep-brain stimulation surgery. The neuroanatomical substrates of posture and gait are poorly understood but a number of important observations suggest a major role for the pedunculopontine nucleus and adjacent areas in the brainstem. We conducted a double-blinded evaluation of unilateral pedunculopontine nucleus deep-brain stimulation in a pilot study in six advanced Parkinson's disease patients with significant gait and postural abnormalities. There was no significant difference in the double-blinded on versus off stimulation Unified Parkinson's Disease Rating Scale motor scores after 3 or 12 months of continuous stimulation and no improvements in the Unified Parkinson's Disease Rating Scale part III scores compared to baseline. In contrast, patients reported a significant reduction in falls in the on and off medication states both at 3 and 12 months after pedunculopontine nucleus deep-brain stimulation as captured in the Unified Parkinson's Disease Rating Scale part II scores. Our results suggest that pedunculopontine nucleus deep-brain stimulation may be effective in preventing falls in patients with advanced Parkinson's disease but that further evaluation of this procedure is required.

Performance on an episodic encoding task yields further insight into functional brain development.

PubMed

McAuley, Tara; Brahmbhatt, Shefali; Barch, Deanna M

2007-01-15

To further characterize changes in functional brain development that are associated with the emergence of cognitive control, participants 14 to 28 years of age were scanned while performing an episodic encoding task with a levels-of-processing manipulation. Using data from the 12 youngest and oldest participants (endpoint groups), 18 regions were identified that showed group differences in task-related activity as a function of processing depth. One region, located in left inferior frontal gyrus, showed enhanced activity in deep relative to shallow encoding that was larger in magnitude for the older group. Seventeen regions showed enhanced activity in shallow relative to deep encoding that was larger in magnitude for the youngest group. These regions were distributed across a broad network that included both cortical and subcortical areas. Regression analyses using the entire sample showed that age made a significant contribution to the difference in beta weights between deep and shallow encoding for 17 of the 18 identified regions in the direction predicted by the endpoint analysis. We conclude that the patterns of brain activation associated with deep and shallow encoding differ between adolescents and young adults in a manner that is consistent with the interactive specialization account of functional brain development.

Real-Time Ultrasound-Guided Catheter Navigation for Approaching Deep-Seated Brain Lesions: Role of Intraoperative Neurosonography with and without Fusion with Magnetic Resonance Imaging.

PubMed

Manjila, Sunil; Karhade, Aditya; Phi, Ji Hoon; Scott, R Michael; Smith, Edward R

2017-01-01

Brain shift during the exposure of cranial lesions may reduce the accuracy of frameless stereotaxy. We describe a rapid, safe, and effective method to approach deep-seated brain lesions using real-time intraoperative ultrasound placement of a catheter to mark the dissection trajectory to the lesion. With Institutional Review Board approval, we retrospectively reviewed the radiographic, pathologic, and intraoperative data of 11 pediatric patients who underwent excision of 12 lesions by means of this technique. Full data sets were available for 12 lesions in 11 patients. Ten lesions were tumors and 2 were cavernous malformations. Lesion locations included the thalamus (n = 4), trigone (n = 3), mesial temporal lobe (n = 3), and deep white matter (n = 2). Catheter placement was successful in all patients, and the median time required for the procedure was 3 min (range 2-5 min). There were no complications related to catheter placement. The median diameter of surgical corridors on postresection magnetic resonance imaging was 6.6 mm (range 3.0-12.1 mm). Use of real-time ultrasound guidance to place a catheter to aid in the dissection to reach a deep-seated brain lesion provides advantages complementary to existing techniques, such as frameless stereotaxy. The catheter insertion technique described here provides a quick, accurate, and safe method for reaching deep-seated lesions. © 2017 S. Karger AG, Basel.

Deep learning and texture-based semantic label fusion for brain tumor segmentation

NASA Astrophysics Data System (ADS)

Vidyaratne, L.; Alam, M.; Shboul, Z.; Iftekharuddin, K. M.

2018-02-01

Brain tumor segmentation is a fundamental step in surgical treatment and therapy. Many hand-crafted and learning based methods have been proposed for automatic brain tumor segmentation from MRI. Studies have shown that these approaches have their inherent advantages and limitations. This work proposes a semantic label fusion algorithm by combining two representative state-of-the-art segmentation algorithms: texture based hand-crafted, and deep learning based methods to obtain robust tumor segmentation. We evaluate the proposed method using publicly available BRATS 2017 brain tumor segmentation challenge dataset. The results show that the proposed method offers improved segmentation by alleviating inherent weaknesses: extensive false positives in texture based method, and the false tumor tissue classification problem in deep learning method, respectively. Furthermore, we investigate the effect of patient's gender on the segmentation performance using a subset of validation dataset. Note the substantial improvement in brain tumor segmentation performance proposed in this work has recently enabled us to secure the first place by our group in overall patient survival prediction task at the BRATS 2017 challenge.

Deep Learning and Texture-Based Semantic Label Fusion for Brain Tumor Segmentation.

PubMed

Vidyaratne, L; Alam, M; Shboul, Z; Iftekharuddin, K M

2018-01-01

Brain tumor segmentation is a fundamental step in surgical treatment and therapy. Many hand-crafted and learning based methods have been proposed for automatic brain tumor segmentation from MRI. Studies have shown that these approaches have their inherent advantages and limitations. This work proposes a semantic label fusion algorithm by combining two representative state-of-the-art segmentation algorithms: texture based hand-crafted, and deep learning based methods to obtain robust tumor segmentation. We evaluate the proposed method using publicly available BRATS 2017 brain tumor segmentation challenge dataset. The results show that the proposed method offers improved segmentation by alleviating inherent weaknesses: extensive false positives in texture based method, and the false tumor tissue classification problem in deep learning method, respectively. Furthermore, we investigate the effect of patient's gender on the segmentation performance using a subset of validation dataset. Note the substantial improvement in brain tumor segmentation performance proposed in this work has recently enabled us to secure the first place by our group in overall patient survival prediction task at the BRATS 2017 challenge.

Resection of a Pediatric Thalamic Juvenile Pilocytic Astrocytoma with Whole Brain Tractography

PubMed Central

Weiner, Howard L

2017-01-01

The resection of deep-seated brain tumors has been associated with morbidity due to injury to critical neural structures during the approach. Recent technological advancements in navigation and stereotaxy, surgical planning, brain tractography and minimal-access brain ports present the opportunity to overcome such limitations. Here, we present the case of a pediatric patient with a left thalamic/midbrain juvenile pilocytic astrocytoma (JPA). The tumor displaced the corticospinal fibers posteriorly and resulted in hemiparesis. Using whole brain tractography to plan a corridor for the approach, neuronavigation, a tubular retractor and an exoscope for visualization, we obtained gross total resection of the tumor, while minimizing injury to white matter bundles, including the corticospinal fibers. We propose that surgical planning with whole brain tractography is essential for reducing morbidity while accessing deep-lying brain lesions via retractor tubes, by means of sparing critical fiber tracts. PMID:29234572

In vivo monitoring of glial scar proliferation on chronically implanted neural electrodes by fiber optical coherence tomography

PubMed Central

Xie, Yijing; Martini, Nadja; Hassler, Christina; Kirch, Robert D.; Stieglitz, Thomas; Seifert, Andreas; Hofmann, Ulrich G.

2014-01-01

In neural prosthetics and stereotactic neurosurgery, intracortical electrodes are often utilized for delivering therapeutic electrical pulses, and recording neural electrophysiological signals. Unfortunately, neuroinflammation impairs the neuron-electrode-interface by developing a compact glial encapsulation around the implants in long term. At present, analyzing this immune reaction is only feasible with post-mortem histology; currently no means for specific in vivo monitoring exist and most applicable imaging modalities can not provide information in deep brain regions. Optical coherence tomography (OCT) is a well established imaging modality for in vivo studies, providing cellular resolution and up to 1.2 mm imaging depth in brain tissue. A fiber based spectral domain OCT was shown to be capable of minimally invasive brain imaging. In the present study, we propose to use a fiber based spectral domain OCT to monitor the progression of the tissue's immune response through scar encapsulation progress in a rat animal model. A fine fiber catheter was implanted in rat brain together with a flexible polyimide microelectrode in sight both of which acts as a foreign body and induces the brain tissue immune reaction. OCT signals were collected from animals up to 12 weeks after implantation and thus gliotic scarring in vivo monitored for that time. Preliminary data showed a significant enhancement of the OCT backscattering signal during the first 3 weeks after implantation, and increased attenuation factor of the sampled tissue due to the glial scar formation. PMID:25191264

Deep Learning MR Imaging-based Attenuation Correction for PET/MR Imaging.

PubMed

Liu, Fang; Jang, Hyungseok; Kijowski, Richard; Bradshaw, Tyler; McMillan, Alan B

2018-02-01

Purpose To develop and evaluate the feasibility of deep learning approaches for magnetic resonance (MR) imaging-based attenuation correction (AC) (termed deep MRAC) in brain positron emission tomography (PET)/MR imaging. Materials and Methods A PET/MR imaging AC pipeline was built by using a deep learning approach to generate pseudo computed tomographic (CT) scans from MR images. A deep convolutional auto-encoder network was trained to identify air, bone, and soft tissue in volumetric head MR images coregistered to CT data for training. A set of 30 retrospective three-dimensional T1-weighted head images was used to train the model, which was then evaluated in 10 patients by comparing the generated pseudo CT scan to an acquired CT scan. A prospective study was carried out for utilizing simultaneous PET/MR imaging for five subjects by using the proposed approach. Analysis of covariance and paired-sample t tests were used for statistical analysis to compare PET reconstruction error with deep MRAC and two existing MR imaging-based AC approaches with CT-based AC. Results Deep MRAC provides an accurate pseudo CT scan with a mean Dice coefficient of 0.971 ± 0.005 for air, 0.936 ± 0.011 for soft tissue, and 0.803 ± 0.021 for bone. Furthermore, deep MRAC provides good PET results, with average errors of less than 1% in most brain regions. Significantly lower PET reconstruction errors were realized with deep MRAC (-0.7% ± 1.1) compared with Dixon-based soft-tissue and air segmentation (-5.8% ± 3.1) and anatomic CT-based template registration (-4.8% ± 2.2). Conclusion The authors developed an automated approach that allows generation of discrete-valued pseudo CT scans (soft tissue, bone, and air) from a single high-spatial-resolution diagnostic-quality three-dimensional MR image and evaluated it in brain PET/MR imaging. This deep learning approach for MR imaging-based AC provided reduced PET reconstruction error relative to a CT-based standard within the brain compared with current MR imaging-based AC approaches. © RSNA, 2017 Online supplemental material is available for this article.

Visualizing Simulated Electrical Fields from Electroencephalography and Transcranial Electric Brain Stimulation: A Comparative Evaluation

PubMed Central

Eichelbaum, Sebastian; Dannhauer, Moritz; Hlawitschka, Mario; Brooks, Dana; Knösche, Thomas R.; Scheuermann, Gerik

2014-01-01

Electrical activity of neuronal populations is a crucial aspect of brain activity. This activity is not measured directly but recorded as electrical potential changes using head surface electrodes (electroencephalogram - EEG). Head surface electrodes can also be deployed to inject electrical currents in order to modulate brain activity (transcranial electric stimulation techniques) for therapeutic and neuroscientific purposes. In electroencephalography and noninvasive electric brain stimulation, electrical fields mediate between electrical signal sources and regions of interest (ROI). These fields can be very complicated in structure, and are influenced in a complex way by the conductivity profile of the human head. Visualization techniques play a central role to grasp the nature of those fields because such techniques allow for an effective conveyance of complex data and enable quick qualitative and quantitative assessments. The examination of volume conduction effects of particular head model parameterizations (e.g., skull thickness and layering), of brain anomalies (e.g., holes in the skull, tumors), location and extent of active brain areas (e.g., high concentrations of current densities) and around current injecting electrodes can be investigated using visualization. Here, we evaluate a number of widely used visualization techniques, based on either the potential distribution or on the current-flow. In particular, we focus on the extractability of quantitative and qualitative information from the obtained images, their effective integration of anatomical context information, and their interaction. We present illustrative examples from clinically and neuroscientifically relevant cases and discuss the pros and cons of the various visualization techniques. PMID:24821532

Neural stimulation for Parkinson's disease: current therapies and future directions.

PubMed

Neimat, Joseph S; Hamani, Clement; Lozano, Andres M

2006-01-01

Neural stimulation has rapidly become an integral tool in the treatment of Parkinson's disease and other movement disorders. Today it serves as an important adjunct to medical therapy that continues to gain applicability to patients in whom the disease has progressed significantly. Studies have demonstrated efficacy in several deep-brain targets, with prolonged benefit exceeding 5-year follow-up times. Continuing study is teaching us more about the mechanism of deep-brain stimulation effect. New targets, which may treat the disease more successfully, are being examined. In this review, the history of deep-brain stimulation, the rationale for the known targets of stimulation; the clinical evidence demonstrating their benefit and, finally, future perspectives on new treatments that are being investigated and may have an impact on the field are discussed.

Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output.

PubMed

Humphries, Mark D; Gurney, Kevin

2012-07-01

Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contributor to the effectiveness of STN DBS. We used our computational model of the complete basal ganglia circuit to show how such a mixture of responses in basal ganglia output naturally arises from the network effects of STN DBS. We replicated the diversification of responses recorded in a primate STN DBS study to show that the model's predicted mixture of responses is consistent with therapeutic STN DBS. We then showed how this 'mixture of response' perspective suggests new ideas for DBS mechanisms: first, that the therapeutic frequency of STN DBS is above 100 Hz because the diversification of responses exhibits a step change above this frequency; and second, that optogenetic models of direct STN stimulation during DBS have proven therapeutically ineffective because they do not replicate the mixture of basal ganglia output responses evoked by electrical DBS. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

A pioneer work on electric brain stimulation in psychotic patients. Rudolph Gottfried Arndt and his 1870s studies.

PubMed

Steinberg, Holger

2013-07-01

Today's brain stimulation methods are commonly traced back historically to surgical brain operations. With this one-sided historical approach it is easy to overlook the fact that non-surgical electrical brain-stimulating applications preceded present-day therapies. The first study on transcranial electrical brain stimulation for the treatment of severe mental diseases in a larger group of patients was carried out in the 1870s. Between 1870 and 1878 German psychiatrist Rudolph Gottfried Arndt published the results of his studies in three reports. These are contextualized with contemporary developments of the time, focusing in particular on the (neuro-) sciences. As was common practice at the time, Arndt basically reported individual cases in which electricity was applied to treat severe psychoses with depressive symptoms or even catatonia, hypochondriac delusion and melancholia. Despite their lengthiness, there is frequently a lack of precise physical data on the application of psychological-psychopathological details. Only his 1878 report includes general rules for electrical brain stimulation. Despite their methodological shortcomings and lack of precise treatment data impeding exact understanding, Arndt's studies are pioneering works in the field of electric brain stimulation with psychoses and its positive impacts. Today's transcranial direct current stimulation, and partly vagus nerve stimulation, can be compared with Arndt's methods. Although Arndt's only tangible results were indications for the application of faradic electricity (for inactivity, stupor, weakness and manic depressions) and galvanic current (for affective disorders and psychoses), a historiography of present-day brain stimulation therapies should no longer neglect studies on electrotherapy published in German and international psychiatric and neurological journals and monographs in the 1870s and 1880s. Copyright © 2013 Elsevier Inc. All rights reserved.

Human Brain Modeling with Its Anatomical Structure and Realistic Material Properties for Brain Injury Prediction.

PubMed

Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami

2018-05-01

Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.

An introduction to neural networks surgery, a field of neuromodulation which is based on advances in neural networks science and digitised brain imaging.

PubMed

Sakas, D E; Panourias, I G; Simpson, B A

2007-01-01

Operative Neuromodulation is the field of altering electrically or chemically the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks and produce therapeutic effects. The present article reviews relevant literature on procedures or devices applied either in contact with the cerebral cortex or cranial nerves or in deep sites inside the brain in order to treat various refractory neurological conditions such as: a) chronic pain (facial, somatic, deafferentation, phantom limb), b) movement disorders (Parkinson's disease, dystonia, Tourette syndrome), c) epilepsy, d) psychiatric disease, e) hearing deficits, and f) visual loss. These data indicate that in operative neuromodulation, a new field emerges that is based on neural networks research and on advances in digitised stereometric brain imaging which allow precise localisation of cerebral neural networks and their relay stations; this field can be described as Neural networks surgery because it aims to act extrinsically or intrinsically on neural networks and to alter therapeutically the neural signal transmission with the use of implantable electrical or electronic devices. The authors also review neurotechnology literature relevant to neuroengineering, nanotechnologies, brain computer interfaces, hybrid cultured probes, neuromimetics, neuroinformatics, neurocomputation, and computational neuromodulation; the latter field is dedicated to the study of the biophysical and mathematical characteristics of electrochemical neuromodulation. The article also brings forward particularly interesting lines of research such as the carbon nanofibers electrode arrays for simultaneous electrochemical recording and stimulation, closed-loop systems for responsive neuromodulation, and the intracortical electrodes for restoring hearing or vision. The present review of cerebral neuromodulatory procedures highlights the transition from the conventional neurosurgery of resective or ablative techniques to a highly selective "surgery of networks". The dynamics of the convergence of the above biomedical and technological fields with biological restorative approaches have important implications for patients with severe neurological disorders.

Brain MRI analysis for Alzheimer's disease diagnosis using an ensemble system of deep convolutional neural networks.

PubMed

Islam, Jyoti; Zhang, Yanqing

2018-05-31

Alzheimer's disease is an incurable, progressive neurological brain disorder. Earlier detection of Alzheimer's disease can help with proper treatment and prevent brain tissue damage. Several statistical and machine learning models have been exploited by researchers for Alzheimer's disease diagnosis. Analyzing magnetic resonance imaging (MRI) is a common practice for Alzheimer's disease diagnosis in clinical research. Detection of Alzheimer's disease is exacting due to the similarity in Alzheimer's disease MRI data and standard healthy MRI data of older people. Recently, advanced deep learning techniques have successfully demonstrated human-level performance in numerous fields including medical image analysis. We propose a deep convolutional neural network for Alzheimer's disease diagnosis using brain MRI data analysis. While most of the existing approaches perform binary classification, our model can identify different stages of Alzheimer's disease and obtains superior performance for early-stage diagnosis. We conducted ample experiments to demonstrate that our proposed model outperformed comparative baselines on the Open Access Series of Imaging Studies dataset.

Temperature profiles in the earth of importance to deep electrical conductivity models

NASA Astrophysics Data System (ADS)

Čermák, Vladimír; Laštovičková, Marcela

1987-03-01

Deep in the Earth, the electrical conductivity of geological material is extremely dependent on temperature. The knowledge of temperature is thus essential for any interpretation of magnetotelluric data in projecting lithospheric structural models. The measured values of the terrestrial heat flow, radiogenic heat production and thermal conductivity of rocks allow the extrapolation of surface observations to a greater depth and the calculation of the temperature field within the lithosphere. Various methods of deep temperature calculations are presented and discussed. Characteristic geotherms are proposed for major tectonic provinces of Europe and it is shown that the existing temperatures on the crust-upper mantle boundary may vary in a broad interval of 350 1,000°C. The present work is completed with a survey of the temperature dependence of electrical conductivity for selected crustal and upper mantle rocks within the interval 200 1,000°C. It is shown how the knowledge of the temperature field can be used in the evaluation of the deep electrical conductivity pattern by converting the conductivity-versustemperature data into the conductivity-versus-depth data.

Effects of Medication and Subthalamic Nucleus Deep Brain Stimulation on Tongue Movements in Speakers with Parkinson's Disease Using Electropalatography: A Pilot Study

ERIC Educational Resources Information Center

Hartinger, Mariam; Tripoliti, Elina; Hardcastle, William J.; Limousin, Patricia

2011-01-01

Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using…

Pitch Variability in Patients with Parkinson's Disease: Effects of Deep Brain Stimulation of Caudal Zona Incerta and Subthalamic Nucleus

ERIC Educational Resources Information Center

Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; van Doorn, Jan

2013-01-01

Purpose: The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of connected speech in patients with Parkinson's disease (PD). Method: The authors evaluated 16 patients preoperatively and 12 months after DBS surgery. Eight…

Articulatory Closure Proficiency in Patients with Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus and Caudal Zona Incerta

ERIC Educational Resources Information Center

Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; Nordh, Erik; van Doorn, Jan

2014-01-01

Purpose: The present study aimed at comparing the effects of deep brain stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) on the proficiency in achieving oral closure and release during plosive production of people with Parkinson's disease. Method: Nineteen patients participated preoperatively and…

Photoinduced current transient spectroscopy of deep levels and transport mechanisms in iron-doped GaN thin films grown by low pressure-metalorganic vapor phase epitaxy

NASA Astrophysics Data System (ADS)

Muret, P.; Pernot, J.; Azize, M.; Bougrioua, Z.

2007-09-01

Electrical transport and deep levels are investigated in GaN:Fe layers epitaxially grown on sapphire by low pressure metalorganic vapor phase epitaxy. Photoinduced current transient spectroscopy and current detected deep level spectroscopy are performed between 200 and 650 K on three Fe-doped samples and an undoped sample. A detailed study of the detected deep levels assigns dominant centers to a deep donor 1.39 eV below the conduction band edge EC and to a deep acceptor 0.75 eV above the valence band edge EV at low electric field. A strong Poole-Frenkel effect is evidenced for the donor. Schottky diodes characteristics and transport properties in the bulk GaN:Fe layer containing a homogenous concentration of 1019 Fe/cm3 are typical of a compensated semiconductor. They both indicate that the bulk Fermi level is located typically 1.4 eV below EC, in agreement with the neutrality equation and dominance of the deep donor concentration. This set of results demonstrates unambiguously that electrical transport in GaN:Fe is governed by both types, either donor or acceptor, of the iron impurity, either substitutional in gallium sites or associated with other defects.

Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation.

PubMed

Hadar, Ravit; Dong, Le; Del-Valle-Anton, Lucia; Guneykaya, Dilansu; Voget, Mareike; Edemann-Callesen, Henriette; Schweibold, Regina; Djodari-Irani, Anais; Goetz, Thomas; Ewing, Samuel; Kettenmann, Helmut; Wolf, Susanne A; Winter, Christine

2017-07-01

In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype. Therapeutic intervention using the anti-inflammatory drug minocycline affected altered microglia activation and was successful in the adult offspring. However, less is known about the effect of preventive therapeutic strategies on microglia properties. Previously we found that deep brain stimulation of the medial prefrontal cortex applied pre-symptomatically to adolescence MIA rats prevented the manifestation of behavioral and structural deficits in adult rats. We here studied the effects of deep brain stimulation during adolescence on microglia properties in adulthood. We found that in the hippocampus and nucleus accumbens, but not in the medial prefrontal cortex, microglial density and soma size were increased in MIA rats. Pro-inflammatory cytokine mRNA was unchanged in all brain areas before and after implantation and stimulation. Stimulation of either the medial prefrontal cortex or the nucleus accumbens normalized microglia density and soma size in main projection areas including the hippocampus and in the area around the electrode implantation. We conclude that in parallel to an alleviation of the symptoms in the rat MIA model, deep brain stimulation has the potential to prevent the neuroinflammatory component in this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

MEASUREMENT OF SMALL MECHANICAL VIBRATIONS OF BRAIN TISSUE EXPOSED TO EXTREMELY-LOW-FREQUENCY ELECTRIC FIELDS

EPA Science Inventory

Electromagnetic fields can interact with biological tissue both electrically and mechanically. This study investigated the mechanical interaction between brain tissue and an extremely-low-frequency (ELF) electric field by measuring the resultant vibrational amplitude. The exposur...

Segmentation of the Globus Pallidus Internus Using Probabilistic Diffusion Tractography for Deep Brain Stimulation Targeting in Parkinson Disease.

PubMed

Middlebrooks, E H; Tuna, I S; Grewal, S S; Almeida, L; Heckman, M G; Lesser, E R; Foote, K D; Okun, M S; Holanda, V M

2018-06-01

Although globus pallidus internus deep brain stimulation is a widely accepted treatment for Parkinson disease, there is persistent variability in outcomes that is not yet fully understood. In this pilot study, we aimed to investigate the potential role of globus pallidus internus segmentation using probabilistic tractography as a supplement to traditional targeting methods. Eleven patients undergoing globus pallidus internus deep brain stimulation were included in this retrospective analysis. Using multidirection diffusion-weighted MR imaging, we performed probabilistic tractography at all individual globus pallidus internus voxels. Each globus pallidus internus voxel was then assigned to the 1 ROI with the greatest number of propagated paths. On the basis of deep brain stimulation programming settings, the volume of tissue activated was generated for each patient using a finite element method solution. For each patient, the volume of tissue activated within each of the 10 segmented globus pallidus internus regions was calculated and examined for association with a change in the Unified Parkinson Disease Rating Scale, Part III score before and after treatment. Increasing volume of tissue activated was most strongly correlated with a change in the Unified Parkinson Disease Rating Scale, Part III score for the primary motor region (Spearman r = 0.74, P = .010), followed by the supplementary motor area/premotor cortex (Spearman r = 0.47, P = .15). In this pilot study, we assessed a novel method of segmentation of the globus pallidus internus based on probabilistic tractography as a supplement to traditional targeting methods. Our results suggest that our method may be an independent predictor of deep brain stimulation outcome, and evaluation of a larger cohort or prospective study is warranted to validate these findings. © 2018 by American Journal of Neuroradiology.

Longitudinal relaxographic imaging of white matter hyperintensities in the elderly

PubMed Central

2014-01-01

Background Incidental white matter hyperintensities (WMHs) are common findings on T2-weighted magnetic resonance images of the aged brain and have been associated with cognitive decline. While a variety of pathogenic mechanisms have been proposed, the origin of WMHs and the extent to which lesions in the deep and periventricular white matter reflect distinct etiologies remains unclear. Our aim was to quantify the fractional blood volume (vb) of small WMHs in vivo using a novel magnetic resonance imaging (MRI) approach and examine the contribution of blood–brain barrier disturbances to WMH formation in the deep and periventricular white matter. Methods Twenty-three elderly volunteers (aged 59–82 years) underwent 7 Tesla relaxographic imaging and fluid-attenuated inversion recovery (FLAIR) MRI. Maps of longitudinal relaxation rate constant (R1) were prepared before contrast reagent (CR) injection and throughout CR washout. Voxelwise estimates of vb were determined by fitting temporal changes in R1 values to a two-site model that incorporates the effects of transendothelial water exchange. Average vb values in deep and periventricular WMHs were determined after semi-automated segmentation of FLAIR images. Ventricular permeability was estimated from the change in CSF R1 values during CR washout. Results In the absence of CR, the total water fraction in both deep and periventricular WMHs was increased compared to normal appearing white matter (NAWM). The vb of deep WMHs was 1.8 ± 0.6 mL/100 g and was significantly reduced compared to NAWM (2.4 ± 0.8 mL/100 g). In contrast, the vb of periventricular WMHs was unchanged compared to NAWM, decreased with ventricular volume and showed a positive association with ventricular permeability. Conclusions Hyperintensities in the deep WM appear to be driven by vascular compromise, while those in the periventricular WM are most likely the result of a compromised ependyma in which the small vessels remain relatively intact. These findings support varying contributions of blood–brain barrier and brain-CSF interface disturbances in the pathophysiology of deep and periventricular WMHs in the aged human brain. PMID:25379172

Transcranial magnetic stimulation of mouse brain using high-resolution anatomical models

NASA Astrophysics Data System (ADS)

Crowther, L. J.; Hadimani, R. L.; Kanthasamy, A. G.; Jiles, D. C.

2014-05-01

Transcranial magnetic stimulation (TMS) offers the possibility of non-invasive treatment of brain disorders in humans. Studies on animals can allow rapid progress of the research including exploring a variety of different treatment conditions. Numerical calculations using animal models are needed to help design suitable TMS coils for use in animal experiments, in particular, to estimate the electric field induced in animal brains. In this paper, we have implemented a high-resolution anatomical MRI-derived mouse model consisting of 50 tissue types to accurately calculate induced electric field in the mouse brain. Magnetic field measurements have been performed on the surface of the coil and compared with the calculations in order to validate the calculated magnetic and induced electric fields in the brain. Results show how the induced electric field is distributed in a mouse brain and allow investigation of how this could be improved for TMS studies using mice. The findings have important implications in further preclinical development of TMS for treatment of human diseases.

Face-Name Association Learning and Brain Structural Substrates in Alcoholism

PubMed Central

Pitel, Anne-Lise; Chanraud, Sandra; Rohlfing, Torsten; Pfefferbaum, Adolf; Sullivan, Edith V.

2011-01-01

Background Associative learning is required for face-name association and is impaired in alcoholism, but the cognitive processes and brain structural components underlying this deficit remain unclear. It is also unknown whether prompting alcoholics to implement a deep level of processing during face-name encoding would enhance performance. Methods Abstinent alcoholics and controls performed a levels-of-processing face-name learning task. Participants indicated whether the face was that of an honest person (deep encoding) or that of a man (shallow encoding). Retrieval was examined using an associative (face-name) recognition task and a single-item (face or name only) recognition task. Participants also underwent a 3T structural MRI. Results Compared with controls, alcoholics had poorer associative and single-item recognition, each impaired to the same extent. Level of processing at encoding had little effect on recognition performance but affected reaction time. Correlations with brain volumes were generally modest and based primarily on reaction time in alcoholics, where the deeper the processing at encoding, the more restricted the correlations with brain volumes. In alcoholics, longer control task reaction times correlated modestly with volumes across several anterior to posterior brain regions; shallow encoding correlated with calcarine and striatal volumes; deep encoding correlated with precuneus and parietal volumes; associative recognition RT correlated with cerebellar volumes. In controls, poorer associative recognition with deep encoding correlated significantly with smaller volumes of frontal and striatal structures. Conclusions Despite prompting, alcoholics did not take advantage of encoding memoranda at a deep level to enhance face-name recognition accuracy. Nonetheless, conditions of deeper encoding resulted in faster reaction times and more specific relations with regional brain volumes than did shallow encoding. The normal relation between associative recognition and corticostriatal volumes was not present in alcoholics. Rather, their speeded reaction time occurred at the expense of accuracy and was related most robustly to cerebellar volumes. PMID:22509954

Face-name association learning and brain structural substrates in alcoholism.

PubMed

Pitel, Anne-Lise; Chanraud, Sandra; Rohlfing, Torsten; Pfefferbaum, Adolf; Sullivan, Edith V

2012-07-01

Associative learning is required for face-name association and is impaired in alcoholism, but the cognitive processes and brain structural components underlying this deficit remain unclear. It is also unknown whether prompting alcoholics to implement a deep level of processing during face-name encoding would enhance performance. Abstinent alcoholics and controls performed a levels-of-processing face-name learning task. Participants indicated whether the face was that of an honest person (deep encoding) or that of a man (shallow encoding). Retrieval was examined using an associative (face-name) recognition task and a single-item (face or name only) recognition task. Participants also underwent 3T structural MRI. Compared with controls, alcoholics had poorer associative and single-item learning and performed at similar levels. Level of processing at encoding had little effect on recognition performance but affected reaction time (RT). Correlations with brain volumes were generally modest and based primarily on RT in alcoholics, where the deeper the processing at encoding, the more restricted the correlations with brain volumes. In alcoholics, longer control task RTs correlated modestly with smaller tissue volumes across several anterior to posterior brain regions; shallow encoding correlated with calcarine and striatal volumes; deep encoding correlated with precuneus and parietal volumes; and associative recognition RT correlated with cerebellar volumes. In controls, poorer associative recognition with deep encoding correlated significantly with smaller volumes of frontal and striatal structures. Despite prompting, alcoholics did not take advantage of encoding memoranda at a deep level to enhance face-name recognition accuracy. Nonetheless, conditions of deeper encoding resulted in faster RTs and more specific relations with regional brain volumes than did shallow encoding. The normal relation between associative recognition and corticostriatal volumes was not present in alcoholics. Rather, their speeded RTs occurred at the expense of accuracy and were related most robustly to cerebellar volumes. Copyright © 2012 by the Research Society on Alcoholism.

[Deep brain stimulation in movement disorders: evidence and therapy standards].

PubMed

Parpaley, Yaroslav; Skodda, Sabine

2017-07-01

The deep brain stimulation (DBS) in movement disorders is well established and in many aspects evidence-based procedure. The treatment indications are very heterogeneous and very specific in their course and therapy. The deep brain stimulation plays very important, but usually not the central role in this conditions. The success in the application of DBS is essentially associated with the correct, appropriate and timely indication of the therapy in the course of these diseases. Thanks to the good standardization of the DBS procedure and sufficient published data, the recommendations for indication, diagnosis and operative procedures can be generated. The following article attempts to summarize the most important decision-making criteria and current therapy standards in this fairly comprehensive subject and to present them in close proximity to practice. Georg Thieme Verlag KG Stuttgart · New York.

Creutzfeldt-Jakob Disease

MedlinePlus

... CJD: Electroencephalogram (EEG) measures the brain's patterns of electrical activity similar to the way an electrocardiogram (ECG) measures the heart's electrical activity. Brain magnetic resonance imaging (MRI) can detect ...

Annotation: What Electrical Brain Activity Tells Us about Brain Function that Other Techniques Cannot Tell Us--A Child Psychiatric Perspective

ERIC Educational Resources Information Center

Banaschewski, Tobias; Brandeis, Daniel

2007-01-01

Background: Monitoring brain processes in real time requires genuine subsecond resolution to follow the typical timing and frequency of neural events. Non-invasive recordings of electric (EEG/ERP) and magnetic (MEG) fields provide this time resolution. They directly measure neural activations associated with a wide variety of brain states and…

Deep brain stimulation in the bed nucleus of the stria terminalis and medial forebrain bundle in a patient with major depressive disorder and anorexia nervosa.

PubMed

Blomstedt, Patric; Naesström, Matilda; Bodlund, Owe

2017-05-01

Deep brain stimulation (DBS) may be considered in severe cases of therapy-refractory major depressive disorder (MDD). However, DBS for MDD is still an experimental therapy. Therefore, it should only be administered in clinical studies driven by multidisciplinary teams, including surgeons with substantial experience of DBS in the treatment of other conditions.

DeepNAT: Deep convolutional neural network for segmenting neuroanatomy.

PubMed

Wachinger, Christian; Reuter, Martin; Klein, Tassilo

2018-04-15

We introduce DeepNAT, a 3D Deep convolutional neural network for the automatic segmentation of NeuroAnaTomy in T1-weighted magnetic resonance images. DeepNAT is an end-to-end learning-based approach to brain segmentation that jointly learns an abstract feature representation and a multi-class classification. We propose a 3D patch-based approach, where we do not only predict the center voxel of the patch but also neighbors, which is formulated as multi-task learning. To address a class imbalance problem, we arrange two networks hierarchically, where the first one separates foreground from background, and the second one identifies 25 brain structures on the foreground. Since patches lack spatial context, we augment them with coordinates. To this end, we introduce a novel intrinsic parameterization of the brain volume, formed by eigenfunctions of the Laplace-Beltrami operator. As network architecture, we use three convolutional layers with pooling, batch normalization, and non-linearities, followed by fully connected layers with dropout. The final segmentation is inferred from the probabilistic output of the network with a 3D fully connected conditional random field, which ensures label agreement between close voxels. The roughly 2.7million parameters in the network are learned with stochastic gradient descent. Our results show that DeepNAT compares favorably to state-of-the-art methods. Finally, the purely learning-based method may have a high potential for the adaptation to young, old, or diseased brains by fine-tuning the pre-trained network with a small training sample on the target application, where the availability of larger datasets with manual annotations may boost the overall segmentation accuracy in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Reliability of temperatures measured at standard monitoring sites as an index of brain temperature during deep hypothermic cardiopulmonary bypass conducted for thoracic aortic reconstruction.

PubMed

Akata, Takashi; Setoguchi, Hidekazu; Shirozu, Kazuhiro; Yoshino, Jun

2007-06-01

It is essential to estimate the brain temperature of patients during deliberate deep hypothermia. Using jugular bulb temperature as a standard for brain temperature, we evaluated the accuracy and precision of 5 standard temperature monitoring sites (ie, pulmonary artery, nasopharynx, forehead deep-tissue, urinary bladder, and fingertip skin-surface tissue) during deep hypothermic cardiopulmonary bypass conducted for thoracic aortic reconstruction. In 20 adult patients with thoracic aortic aneurysms, the 5 temperature monitoring sites were recorded every 1 minute during deep hypothermic (<20 degrees C) cardiopulmonary bypass. The accuracy was evaluated by the difference from jugular bulb temperature, and the precision was evaluated by its standard deviation, as well as by the correlation with jugular bulb temperature. Pulmonary artery temperature and jugular bulb temperature began to change immediately after the start of cooling or rewarming, closely matching each other, and the other temperatures lagged behind these two temperatures. During either situation, the accuracy of pulmonary artery temperature measurement (0.3 degrees C-0.5 degrees C) was much superior to the other measurements, and its precision (standard deviation of the difference from jugular bulb temperature = 1.5 degrees C-1.8 degrees C; correlation coefficient = 0.94-0.95) was also best among the measurements, with its rank order being pulmonary artery > or = nasopharynx > forehead > bladder > fingertip. However, the accuracy and precision of pulmonary artery temperature measurement was significantly impaired during and for several minutes after infusion of cold cardioplegic solution. Pulmonary artery temperature measurement is recommended to estimate brain temperature during deep hypothermic cardiopulmonary bypass, even if it is conducted with the sternum opened; however, caution needs to be exercised in interpreting its measurements during periods of the cardioplegic solution infusion.

Fiber-based tissue identification for electrode placement in deep brain stimulation neurosurgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

DePaoli, Damon T.; Lapointe, Nicolas; Goetz, Laurent; Parent, Martin; Prudhomme, Michel; Cantin, Léo.; Galstian, Tigran; Messaddeq, Younès.; Côté, Daniel C.

2016-03-01

Deep brain stimulation's effectiveness relies on the ability of the stimulating electrode to be properly placed within a specific target area of the brain. Optical guidance techniques that can increase the accuracy of the procedure, without causing any additional harm, are therefore of great interest. We have designed a cheap optical fiber-based device that is small enough to be placed within commercially available DBS stimulating electrodes' hollow cores and that is capable of sensing biological information from the surrounding tissue, using low power white light. With this probe we have shown the ability to distinguish white and grey matter as well as blood vessels, in vitro, in human brain samples and in vivo, in rats. We have also repeated the in vitro procedure with the probe inserted in a DBS stimulating electrode and found the results were in good agreement. We are currently validating a second fiber optic device, with micro-optical components, that will result in label free, molecular level sensing capabilities, using CARS spectroscopy. The final objective will be to use this data in real time, during deep brain stimulation neurosurgery, to increase the safety and accuracy of the procedure.

Left temporal and temporoparietal brain activity depends on depth of word encoding: a magnetoencephalographic study in healthy young subjects.

PubMed

Walla, P; Hufnagl, B; Lindinger, G; Imhof, H; Deecke, L; Lang, W

2001-03-01

Using a 143-channel whole-head magnetoencephalograph (MEG) we recorded the temporal changes of brain activity from 26 healthy young subjects (14 females) related to shallow perceptual and deep semantic word encoding. During subsequent recognition tests, the subjects had to recognize the previously encoded words which were interspersed with new words. The resulting mean memory performances across all subjects clearly mirrored the different levels of encoding. The grand averaged event-related fields (ERFs) associated with perceptual and semantic word encoding differed significantly between 200 and 550 ms after stimulus onset mainly over left superior temporal and left superior parietal sensors. Semantic encoding elicited higher brain activity than perceptual encoding. Source localization procedures revealed that neural populations of the left temporal and temporoparietal brain areas showed different activity strengths across the whole group of subjects depending on depth of word encoding. We suggest that the higher brain activity associated with deep encoding as compared to shallow encoding was due to the involvement of more neural systems during the processing of visually presented words. Deep encoding required more energy than shallow encoding but for all that led to a better memory performance. Copyright 2001 Academic Press.

Brain hemorrhage after electrical burn injury: Case report and probable mechanism.

PubMed

Axayacalt, Gutierrez Aceves Guillermo; Alejandro, Ceja Espinosa; Marcos, Rios Alanis; Inocencio, Ruiz Flores Milton; Alfredo, Herrera Gonzalez Jose

2016-01-01

High-voltage electric injury may induce lesion in different organs. In addition to the local tissue damage, electrical injuries may lead to neurological deficits, musculoskeletal damage, and cardiovascular injury. Severe vascular damage may occur making the blood vessels involved prone to thrombosis and spontaneous rupture. Here, we present the case of a 39-year-old male who suffered an electrical burn with high tension wire causing intracranial bleeding. He presented with an electrical burn in the parietal area (entry zone) and the left forearm (exit zone). The head tomography scan revealed an intraparenchimatous bleeding in the left parietal area. In this case, the electric way was the scalp, cranial bone, blood vessels and brain, upper limb muscle, and skin. The damage was different according to the dielectric property in each tissue. The injury was in the scalp, cerebral blood vessel, skeletal muscle, and upper limb skin. The main damage was in brain's blood vessels because of the dielectric and geometric features that lead to bleeding, high temperature, and gas delivering. This is a report of a patient with an electric brain injury that can be useful to elucidate the behavior of the high voltage electrical current flow into the nervous system.

Fiberless multicolor neural optoelectrode for in vivo circuit analysis

PubMed Central

Kampasi, Komal; Stark, Eran; Seymour, John; Na, Kyounghwan; Winful, Herbert G.; Buzsáki, György; Wise, Kensall D.; Yoon, Euisik

2016-01-01

Maximizing the potential of optogenetic approaches in deep brain structures of intact animals requires optical manipulation of neurons at high spatial and temporal resolutions, while simultaneously recording electrical data from those neurons. Here, we present the first fiber-less optoelectrode with a monolithically integrated optical waveguide mixer that can deliver multicolor light at a common waveguide port to achieve multicolor modulation of the same neuronal population in vivo. We demonstrate successful device implementation by achieving efficient coupling between a side-emitting injection laser diode (ILD) and a dielectric optical waveguide mixer via a gradient-index (GRIN) lens. The use of GRIN lenses attains several design features, including high optical coupling and thermal isolation between ILDs and waveguides. We validated the packaged devices in the intact brain of anesthetized mice co-expressing Channelrhodopsin-2 and Archaerhodopsin in pyramidal cells in the hippocampal CA1 region, achieving high quality recording, activation and silencing of the exact same neurons in a given local region. This fully-integrated approach demonstrates the spatial precision and scalability needed to enable independent activation and silencing of the same or different groups of neurons in dense brain regions while simultaneously recording from them, thus considerably advancing the capabilities of currently available optogenetic toolsets. PMID:27485264

Importance of extended spatial coverage for quantitative susceptibility mapping of iron-rich deep gray matter.

PubMed

Elkady, Ahmed M; Sun, Hongfu; Wilman, Alan H

2016-05-01

Quantitative Susceptibility Mapping (QSM) is an emerging area of brain research with clear application to brain iron studies in deep gray matter. However, acquisition of standard whole brain QSM can be time-consuming. One means to reduce scan time is to use a focal acquisition restricted only to the regions of interest such as deep gray matter. However, the non-local dipole field necessary for QSM reconstruction extends far beyond the structure of interest. We demonstrate the practical implications of these non-local fields on the choice of brain volume for QSM. In an illustrative numerical simulation and then in human brain experiments, we examine the effect on QSM of volume reduction in each dimension. For the globus pallidus, as an example of iron-rich deep gray matter, we demonstrate that substantial errors can arise even when the field-of-view far exceeds the physical structural boundaries. Thus, QSM reconstruction requires a non-local field-of-view prescription to ensure minimal errors. An axial QSM acquisition, centered on the globus pallidus, should encompass at least 76mm in the superior-inferior direction to conserve susceptibility values from the globus pallidus. This dimension exceeds the physical coronal extent of this structure by at least five-fold. As QSM sees wider use in the neuroscience community, its unique requirement for an extended field-of-view needs to be considered. Copyright © 2016 Elsevier Inc. All rights reserved.

Cognitive Activation by Central Thalamic Stimulation: The Yerkes-Dodson Law Revisited.

PubMed Central

Mair, Robert G.; Onos, Kristen D.; Hembrook, Jacqueline R.

2011-01-01

Central thalamus regulates forebrain arousal, influencing activity in distributed neural networks that give rise to organized actions during alert, wakeful states. Central thalamus has been implicated in working memory by the effects of lesions and microinjected drugs in this part of the brain. Lesions and drugs that inhibit neural activity have been found to impair working memory. Drugs that increase activity have been found to enhance and impair memory depending on the dose tested. Electrical deep brain stimulation (DBS) similarly enhances working memory at low stimulating currents and impairs it at higher currents. These effects are time dependent. They were observed when DBS was applied during the memory delay (retention) or choice response (retrieval) but not earlier in trials during the sample (acquisition) phase. The effects of microinjected drugs and DBS are consistent with the Yerkes-Dodson law, which describes an inverted-U relationship between arousal and behavioral performance. Alternatively these results may reflect desensitization associated with higher levels of stimulation, spread of drugs or current to adjacent structures, or activation of less sensitive neurons or receptors at higher DBS currents or drug doses. PMID:22013395

Anticipatory activity in the human thalamus is predictive of reaction times.

PubMed

Nikulin, V V; Marzinzik, F; Wahl, M; Schneider, G-H; Kupsch, A; Curio, G; Klostermann, F

2008-09-09

Responding to environmental stimuli in a fast manner is a fundamental behavioral capacity. The pace at which one responds is known to be predetermined by cortical areas, but it remains to be shown if subcortical structures also take part in defining motor swiftness. As the thalamus has previously been implicated in behavioral control, we tested if neuronal activity at this level could also predict the reaction time of upcoming movements. To this end we simultaneously recorded electrical brain activity from the scalp and the ventral intermediate nucleus (VIM) of the thalamus in patients undergoing thalamic deep brain stimulation. Based on trial-to-trial analysis of a Go/NoGo task, we demonstrate that both cortical and thalamic neuronal activity prior to the delivery of upcoming Go stimulus correlates with the reaction time. This result goes beyond the demonstration of thalamic activity being associated with but potentially staying invariant to motor performance. In contrast, it indicates that the latencies at which we respond to environmental stimuli are not exclusively related to cortical pre-movement states but are also correlated with anticipatory thalamic activity.

In vitro and in vivo evaluation of poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate)/dopamine-coated electrodes for dopamine delivery.

PubMed

Sui, L; Song, X J; Ren, J; Cai, W J; Ju, L H; Wang, Y; Wang, L Y; Chen, M

2014-06-01

Poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly(styrene sulfonate) (PSS) has a variety of chemical and biomedical applications. The application of PEDOT/PSS polymers in drug delivery has attracted attention. However, whether conducting polymers of PEDOT/PSS could be used for dopamine delivery has not clear. In the present study, the PEDOT/PSS coatings incorporated with dopamine were fabricated on 0.5 mm diameter platinum electrodes, electrochemical properties, and dopamine delivery capacities of these electrodes were evaluated in vitro and in vivo through implanting these electrodes into brain striatum area. The findings demonstrated that the PEDOT/PSS/dopamine coatings on platinum electrodes could reduce electrodes impedances, increase charge storage capacities, and release significant levels of dopamine upon electrical stimulation of these electrodes. These results indicated that polymers of PEDOT/PSS/dopamine could be used for dopamine delivery, implicating potential application of PEDOT/PSS/dopamine-coated implantable electrodes in the treatment of some diseases associated with dopamine deficits, such as, electrodes for the treatment of Parkinson's disease during deep brain stimulation. Copyright © 2013 Wiley Periodicals, Inc.

Design and optimization of an ultra wideband and compact microwave antenna for radiometric monitoring of brain temperature.

PubMed

Rodrigues, Dario B; Maccarini, Paolo F; Salahi, Sara; Oliveira, Tiago R; Pereira, Pedro J S; Limao-Vieira, Paulo; Snow, Brent W; Reudink, Doug; Stauffer, Paul R

2014-07-01

We present the modeling efforts on antenna design and frequency selection to monitor brain temperature during prolonged surgery using noninvasive microwave radiometry. A tapered log-spiral antenna design is chosen for its wideband characteristics that allow higher power collection from deep brain. Parametric analysis with the software HFSS is used to optimize antenna performance for deep brain temperature sensing. Radiometric antenna efficiency (η) is evaluated in terms of the ratio of power collected from brain to total power received by the antenna. Anatomical information extracted from several adult computed tomography scans is used to establish design parameters for constructing an accurate layered 3-D tissue phantom. This head phantom includes separate brain and scalp regions, with tissue equivalent liquids circulating at independent temperatures on either side of an intact skull. The optimized frequency band is 1.1-1.6 GHz producing an average antenna efficiency of 50.3% from a two turn log-spiral antenna. The entire sensor package is contained in a lightweight and low-profile 2.8 cm diameter by 1.5 cm high assembly that can be held in place over the skin with an electromagnetic interference shielding adhesive patch. The calculated radiometric equivalent brain temperature tracks within 0.4 °C of the measured brain phantom temperature when the brain phantom is lowered 10 °C and then returned to the original temperature (37 °C) over a 4.6-h experiment. The numerical and experimental results demonstrate that the optimized 2.5-cm log-spiral antenna is well suited for the noninvasive radiometric sensing of deep brain temperature.

Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf

NASA Astrophysics Data System (ADS)

Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; An Nguyen, Thien; Alfano, Robert R.

2014-06-01

Two-photon (2P) excitation of the second singlet (S) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S2 state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf.

PubMed

Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; Nguyen, Thien An; Alfano, Robert R

2014-06-01

Two-photon (2P) excitation of the second singlet (S₂) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S₂ state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S₂ state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

Progress to a Gallium-Arsenide Deep-Center Laser

PubMed Central

Pan, Janet L.

2009-01-01

Although photoluminescence from gallium-arsenide (GaAs) deep-centers was first observed in the 1960s, semiconductor lasers have always utilized conduction-to-valence-band transitions. Here we review recent materials studies leading to the first GaAs deep-center laser. First, we summarize well-known properties: nature of deep-center complexes, Franck-Condon effect, photoluminescence. Second, we describe our recent work: insensitivity of photoluminescence with heating, striking differences between electroluminescence and photoluminescence, correlation between transitions to deep-states and absence of bandgap-emission. Room-temperature stimulated-emission from GaAs deep-centers was observed at low electrical injection, and could be tuned from the bandgap to half-the-bandgap (900–1,600 nm) by changing the electrical injection. The first GaAs deep-center laser was demonstrated with electrical injection, and exhibited a threshold of less than 27 mA/cm2 in continuous-wave mode at room temperature at the important 1.54 μm fiber-optic wavelength. This small injection for laser action was explained by fast depopulation of the lower state of the optical transition (fast capture of free holes onto deep-centers), which maintains the population inversion. The evidence for laser action included: superlinear L-I curve, quasi-Fermi level separations satisfying Bernard-Duraffourg’s criterion, optical gains larger than known significant losses, clamping of the optical-emission from lossy modes unable to reach laser action, pinning of the population distribution during laser action.

Low Cost Electric Propulsion Thruster for Deep Space Robotic Science Missions

NASA Technical Reports Server (NTRS)

Manzella, David

2008-01-01

Electric Propulsion (EP) has found widespread acceptance by commercial satellite providers for on-orbit station keeping due to the total life cycle cost advantages these systems offer. NASA has also sought to benefit from the use of EP for primary propulsion onboard the Deep Space-1 and DAWN spacecraft. These applications utilized EP systems based on gridded ion thrusters, which offer performance unequaled by other electric propulsion thrusters. Through the In-Space Propulsion Project, a lower cost thruster technology is currently under development designed to make electric propulsion intended for primary propulsion applications cost competitive with chemical propulsion systems. The basis for this new technology is a very reliable electric propulsion thruster called the Hall thruster. Hall thrusters, which have been flown by the Russians dating back to the 1970s, have been used by the Europeans on the SMART-1 lunar orbiter and currently employed by 15 other geostationary spacecraft. Since the inception of the Hall thruster, over 100 of these devices have been used with no known failures. This paper describes the latest accomplishments of a development task that seeks to improve Hall thruster technology by increasing its specific impulse, throttle-ability, and lifetime to make this type of electric propulsion thruster applicable to NASA deep space science missions. In addition to discussing recent progress on this task, this paper describes the performance and cost benefits projected to result from the use of advanced Hall thrusters for deep space science missions.

Volumetric Radiosurgery for 1 to 10 Brain Metastases: A Multicenter, Single-Arm, Phase 2 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichol, Alan, E-mail: anichol@bccancer.bc.ca; University of British Columbia, Vancouver, British Columbia; Ma, Roy

Purpose: Interest is growing in treating multiple brain metastases with radiosurgery. We report on the effectiveness and tolerability of volumetric radiosurgery (VRS). Methods and Materials: We enrolled patients with a ≥6-month estimated life expectancy and 1 to 10 brain metastases with a diameter of ≤3 cm at 5 cancer centers. Volumetric radiosurgery was delivered in 5 fractions with 98% target coverage, prescribed as 95% of 50 Gy (47.5 Gy in 5 fractions) to the metastases with no margin and 95% of 40 Gy (38 Gy in 5 fractions) to their 2-mm planning target volumes, concurrent with 20 Gy to the whole brain planning target volume. The treatmentmore » was delivered with daily image guidance using conventional linear accelerators and volumetric modulated arc therapy. A magnetic resonance imaging scan was obtained every 3 months. The primary endpoint was the 3-month objective response in the brain according to the Response Evaluation Criteria in Solid Tumors, version 1.1. The principal secondary endpoint was 1-year actuarial control of treated metastases. Toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. The present study is registered with (ClinicalTrials.gov) ( (clinicaltrials.gov) identifier (NCT01046123)). Results: From July 2010 to May 2013, 60 patients underwent VRS with 47.5 Gy in 5 fractions for 12 metastases in the thalamus and basal ganglia (deep metastases) and 207 non-deep metastases. The median follow-up period was 30.5 months, and the median survival was 10.1 months. For the 43 patients assessable at 3 months, the objective response in the brain was 56%. The treated metastases were controlled in 88% of patients at 1 year and 84% at 3 years. Overall survival did not differ for patients with 4 to 10 versus 1 to 3 metastases (hazard ratio 1.18, P=.6). The crude incidence of severe radionecrosis (grade 3-5) was 25% (3 of 12) per deep metastasis, 1.9% (4 of 219) per non-deep metastasis, and 10% (6 of 60) per patient. Conclusions: For non-deep brain metastases, 47.5 Gy in 5 fractions was tolerable. Volumetric radiosurgery was effective for long-term control of treated brain metastases.« less

Predicting the Electric Field Distribution in the Brain for the Treatment of Glioblastoma

PubMed Central

Miranda, Pedro C.; Mekonnen, Abeye; Salvador, Ricardo; Basser, Peter J.

2014-01-01

The use of alternating electric fields has been recently proposed for the treatment of recurrent glioblastoma. In order to predict the electric field distribution in the brain during the application of such tumor treating fields (TTF), we constructed a realistic head model from MRI data and placed transducer arrays on the scalp to mimic an FDA-approved medical device. Values for the tissue dielectric properties were taken from the literature; values for the device parameters were obtained from the manufacturer. The finite element method was used to calculate the electric field distribution in the brain. We also included a “virtual lesion” in the model to simulate the presence of an idealized tumor. The calculated electric field in the brain varied mostly between 0.5 and 2.0 V/cm and exceeded 1.0 V/cm in 60% of the total brain volume. Regions of local field enhancement occurred near interfaces between tissues with different conductivities wherever the electric field was perpendicular to those interfaces. These increases were strongest near the ventricles but were also present outside the tumor’s necrotic core and in some parts of the gray matter-white matter interface. The electric field values predicted in this model brain are in reasonably good agreement with those that have been shown to reduce cancer cell proliferation in vitro. The electric field distribution is highly non-uniform and depends on tissue geometry and dielectric properties. This could explain some of the variability in treatment outcomes. The proposed modeling framework could be used to better understand the physical basis of TTF efficacy through retrospective analysis and to improve TTF treatment planning. PMID:25003941

Predicting the electric field distribution in the brain for the treatment of glioblastoma

NASA Astrophysics Data System (ADS)

Miranda, Pedro C.; Mekonnen, Abeye; Salvador, Ricardo; Basser, Peter J.

2014-08-01

The use of alternating electric fields has been recently proposed for the treatment of recurrent glioblastoma. In order to predict the electric field distribution in the brain during the application of such tumor treating fields (TTF), we constructed a realistic head model from MRI data and placed transducer arrays on the scalp to mimic an FDA-approved medical device. Values for the tissue dielectric properties were taken from the literature; values for the device parameters were obtained from the manufacturer. The finite element method was used to calculate the electric field distribution in the brain. We also included a ‘virtual lesion’ in the model to simulate the presence of an idealized tumor. The calculated electric field in the brain varied mostly between 0.5 and 2.0 V cm - 1 and exceeded 1.0 V cm - 1 in 60% of the total brain volume. Regions of local field enhancement occurred near interfaces between tissues with different conductivities wherever the electric field was perpendicular to those interfaces. These increases were strongest near the ventricles but were also present outside the tumor’s necrotic core and in some parts of the gray matter-white matter interface. The electric field values predicted in this model brain are in reasonably good agreement with those that have been shown to reduce cancer cell proliferation in vitro. The electric field distribution is highly non-uniform and depends on tissue geometry and dielectric properties. This could explain some of the variability in treatment outcomes. The proposed modeling framework could be used to better understand the physical basis of TTF efficacy through retrospective analysis and to improve TTF treatment planning.

Predicting the electric field distribution in the brain for the treatment of glioblastoma.

PubMed

Miranda, Pedro C; Mekonnen, Abeye; Salvador, Ricardo; Basser, Peter J

2014-08-07

The use of alternating electric fields has been recently proposed for the treatment of recurrent glioblastoma. In order to predict the electric field distribution in the brain during the application of such tumor treating fields (TTF), we constructed a realistic head model from MRI data and placed transducer arrays on the scalp to mimic an FDA-approved medical device. Values for the tissue dielectric properties were taken from the literature; values for the device parameters were obtained from the manufacturer. The finite element method was used to calculate the electric field distribution in the brain. We also included a 'virtual lesion' in the model to simulate the presence of an idealized tumor. The calculated electric field in the brain varied mostly between 0.5 and 2.0 V cm( - 1) and exceeded 1.0 V cm( - 1) in 60% of the total brain volume. Regions of local field enhancement occurred near interfaces between tissues with different conductivities wherever the electric field was perpendicular to those interfaces. These increases were strongest near the ventricles but were also present outside the tumor's necrotic core and in some parts of the gray matter-white matter interface. The electric field values predicted in this model brain are in reasonably good agreement with those that have been shown to reduce cancer cell proliferation in vitro. The electric field distribution is highly non-uniform and depends on tissue geometry and dielectric properties. This could explain some of the variability in treatment outcomes. The proposed modeling framework could be used to better understand the physical basis of TTF efficacy through retrospective analysis and to improve TTF treatment planning.

Glioblastoma recurrence correlates with NLGN3 levels.

PubMed

Liu, Rui; Qin, Xing-Ping; Zhuang, Yang; Zhang, Ya; Liao, Hua-Bao; Tang, Jun-Chun; Pan, Meng-Xian; Zeng, Fei-Fei; Lei, Yang; Lei, Rui-Xue; Wang, Shu; Liu, An-Chun; Chen, Juan; Zhang, Zhi-Feng; Zhao, Dan; Wu, Song-Lin; Liu, Ren-Zhong; Wang, Ze-Fen; Wan, Qi

2018-05-18

Glioblastoma (GBM) is the most aggressive glioma in the brain. Recurrence of GBM is almost inevitable within a short term after tumor resection. In a retrospective study of 386 cases of GBM collected between 2013 and 2016, we found that recurrence of GBM mainly occurs in the deep brain regions, including the basal ganglia, thalamus, and corpus callosum. But the mechanism underlying this phenomenon is not clear. Previous studies suggest that neuroligin-3 (NLGN3) is necessary for GBM growth. Our results show that the levels of NLGN3 in the cortex are higher than those in the deep regions in a normal human brain, and similar patterns are also found in a normal mouse brain. In contrast, NLGN3 levels in the deep brain regions of GBM patients are high. We also show that an increase in NLGN3 concentration promotes the growth of U251 cells and U87-MG cells. Respective use of the cortex neuron culture medium (C-NCM) and basal ganglia neuron culture medium (BG-NCM) with DMEM to cultivate U251, U87-MG and GBM cells isolated from patients, we found that these cells grew faster after treatment with C-NCM and BG-NCM in which the cells treated with C-NCM grew faster than the ones treated with BG-NCM group. Inhibition of NLGN3 release by ADAM10i prevents NCM-induced cell growth. Together, this study suggests that increased levels of NLGN3 in the deep brain region under the GBM pathological circumstances may contribute to GBM recurrence in the basal ganglia, thalamus, and corpus callosum. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Efficacy of brain-computer interface-driven neuromuscular electrical stimulation for chronic paresis after stroke.

PubMed

Mukaino, Masahiko; Ono, Takashi; Shindo, Keiichiro; Fujiwara, Toshiyuki; Ota, Tetsuo; Kimura, Akio; Liu, Meigen; Ushiba, Junichi

2014-04-01

Brain computer interface technology is of great interest to researchers as a potential therapeutic measure for people with severe neurological disorders. The aim of this study was to examine the efficacy of brain computer interface, by comparing conventional neuromuscular electrical stimulation and brain computer interface-driven neuromuscular electrical stimulation, using an A-B-A-B withdrawal single-subject design. A 38-year-old male with severe hemiplegia due to a putaminal haemorrhage participated in this study. The design involved 2 epochs. In epoch A, the patient attempted to open his fingers during the application of neuromuscular electrical stimulation, irrespective of his actual brain activity. In epoch B, neuromuscular electrical stimulation was applied only when a significant motor-related cortical potential was observed in the electroencephalogram. The subject initially showed diffuse functional magnetic resonance imaging activation and small electro-encephalogram responses while attempting finger movement. Epoch A was associated with few neurological or clinical signs of improvement. Epoch B, with a brain computer interface, was associated with marked lateralization of electroencephalogram (EEG) and blood oxygenation level dependent responses. Voluntary electromyogram (EMG) activity, with significant EEG-EMG coherence, was also prompted. Clinical improvement in upper-extremity function and muscle tone was observed. These results indicate that self-directed training with a brain computer interface may induce activity- dependent cortical plasticity and promote functional recovery. This preliminary clinical investigation encourages further research using a controlled design.

Characterizing Deep Brain Stimulation effects in computationally efficient neural network models.

PubMed

Latteri, Alberta; Arena, Paolo; Mazzone, Paolo

2011-04-15

Recent studies on the medical treatment of Parkinson's disease (PD) led to the introduction of the so called Deep Brain Stimulation (DBS) technique. This particular therapy allows to contrast actively the pathological activity of various Deep Brain structures, responsible for the well known PD symptoms. This technique, frequently joined to dopaminergic drugs administration, replaces the surgical interventions implemented to contrast the activity of specific brain nuclei, called Basal Ganglia (BG). This clinical protocol gave the possibility to analyse and inspect signals measured from the electrodes implanted into the deep brain regions. The analysis of these signals led to the possibility to study the PD as a specific case of dynamical synchronization in biological neural networks, with the advantage to apply the theoretical analysis developed in such scientific field to find efficient treatments to face with this important disease. Experimental results in fact show that the PD neurological diseases are characterized by a pathological signal synchronization in BG. Parkinsonian tremor, for example, is ascribed to be caused by neuron populations of the Thalamic and Striatal structures that undergo an abnormal synchronization. On the contrary, in normal conditions, the activity of the same neuron populations do not appear to be correlated and synchronized. To study in details the effect of the stimulation signal on a pathological neural medium, efficient models of these neural structures were built, which are able to show, without any external input, the intrinsic properties of a pathological neural tissue, mimicking the BG synchronized dynamics.We start considering a model already introduced in the literature to investigate the effects of electrical stimulation on pathologically synchronized clusters of neurons. This model used Morris Lecar type neurons. This neuron model, although having a high level of biological plausibility, requires a large computational effort to simulate large scale networks. For this reason we considered a reduced order model, the Izhikevich one, which is computationally much lighter. The comparison between neural lattices built using both neuron models provided comparable results, both without traditional stimulation and in presence of all the stimulation protocols. This was a first result toward the study and simulation of the large scale neural networks involved in pathological dynamics.Using the reduced order model an inspection on the activity of two neural lattices was also carried out at the aim to analyze how the stimulation in one area could affect the dynamics in another area, like the usual medical treatment protocols require.The study of population dynamics that was carried out allowed us to investigate, through simulations, the positive effects of the stimulation signals in terms of desynchronization of the neural dynamics. The results obtained constitute a significant added value to the analysis of synchronization and desynchronization effects due to neural stimulation. This work gives the opportunity to more efficiently study the effect of stimulation in large scale yet computationally efficient neural networks. Results were compared both with the other mathematical models, using Morris Lecar and Izhikevich neurons, and with simulated Local Field Potentials (LFP).

Technical nuances to minimize common complications of deep brain stimulation.

PubMed

House, Paul

2017-04-01

The implantation of deep brain stimulator electrodes is associated with infrequent complications. These complications are consistent across prospective trials and include infection, skin erosion, hemorrhage, and lead misplacement. Nuances of surgical technique can be used to minimize the risk of these commonly noted complications. Several of these technical nuances are highlighted in this video submission. The video can be found here: https://youtu.be/GL09W9p013g .

Confocal multispot microscope for fast and deep imaging in semicleared tissues

NASA Astrophysics Data System (ADS)

Adam, Marie-Pierre; Müllenbroich, Marie Caroline; Di Giovanna, Antonino Paolo; Alfieri, Domenico; Silvestri, Ludovico; Sacconi, Leonardo; Pavone, Francesco Saverio

2018-02-01

Although perfectly transparent specimens are imaged faster with light-sheet microscopy, less transparent samples are often imaged with two-photon microscopy leveraging its robustness to scattering; however, at the price of increased acquisition times. Clearing methods that are capable of rendering strongly scattering samples such as brain tissue perfectly transparent specimens are often complex, costly, and time intensive, even though for many applications a slightly lower level of tissue transparency is sufficient and easily achieved with simpler and faster methods. Here, we present a microscope type that has been geared toward the imaging of semicleared tissue by combining multispot two-photon excitation with rolling shutter wide-field detection to image deep and fast inside semicleared mouse brain. We present a theoretical and experimental evaluation of the point spread function and contrast as a function of shutter size. Finally, we demonstrate microscope performance in fixed brain slices by imaging dendritic spines up to 400-μm deep.

Brain Tumor Segmentation Using Deep Belief Networks and Pathological Knowledge.

PubMed

Zhan, Tianming; Chen, Yi; Hong, Xunning; Lu, Zhenyu; Chen, Yunjie

2017-01-01

In this paper, we propose an automatic brain tumor segmentation method based on Deep Belief Networks (DBNs) and pathological knowledge. The proposed method is targeted against gliomas (both low and high grade) obtained in multi-sequence magnetic resonance images (MRIs). Firstly, a novel deep architecture is proposed to combine the multi-sequences intensities feature extraction with classification to get the classification probabilities of each voxel. Then, graph cut based optimization is executed on the classification probabilities to strengthen the spatial relationships of voxels. At last, pathological knowledge of gliomas is applied to remove some false positives. Our method was validated in the Brain Tumor Segmentation Challenge 2012 and 2013 databases (BRATS 2012, 2013). The performance of segmentation results demonstrates our proposal providing a competitive solution with stateof- the-art methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cognitive assessment instruments in Parkinson's disease patients undergoing deep brain stimulation

PubMed Central

Romann, Aline Juliane; Dornelles, Silvia; Maineri, Nicole de Liz; Rieder, Carlos Roberto de Mello; Olchik, Maira Rozenfeld

2012-01-01

Deep Brain Stimulation (DBS) is a widely used surgical technique in individuals with Parkinson's disease (PD) that can lead to significant reductions in motor symptoms. Objectives To determine, from publications, the most commonly used instruments for cognitive evaluation of individuals with PD undergoing DBS. Methods A systematic review of the databases: PubMed, Medline, EBECS, Scielo and LILACS was conducted, using the descriptors "Deep Brain Stimulation", "Verbal Fluency", "Parkinson Disease", "Executive Function", "Cognition" and "Cognitive Assessment" in combination. Results The Verbal Fluency test was found to be the most used instrument for this investigation in the studies, followed by the Boston Naming Test. References to the Stroop Test, Trail Making Test, and Rey's Auditory Verbal Learning Test were also found. Conclusions The validation of instruments for this population is needed as is the use of batteries offering greater specificity and sensitivity for the detection of cognitive impairment. PMID:29213766

A PC-based system for predicting movement from deep brain signals in Parkinson's disease.

PubMed

Loukas, Constantinos; Brown, Peter

2012-07-01

There is much current interest in deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the treatment of Parkinson's disease (PD). This type of surgery has enabled unprecedented access to deep brain signals in the awake human. In this paper we present an easy-to-use computer based system for recording, displaying, archiving, and processing electrophysiological signals from the STN. The system was developed for predicting self-paced hand-movements in real-time via the online processing of the electrophysiological activity of the STN. It is hoped that such a computerised system might have clinical and experimental applications. For example, those sites within the STN most relevant to the processing of voluntary movement could be identified through the predictive value of their activities with respect to the timing of future movement. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Automated deep-phenotyping of the vertebrate brain

PubMed Central

Allalou, Amin; Wu, Yuelong; Ghannad-Rezaie, Mostafa; Eimon, Peter M; Yanik, Mehmet Fatih

2017-01-01

Here, we describe an automated platform suitable for large-scale deep-phenotyping of zebrafish mutant lines, which uses optical projection tomography to rapidly image brain-specific gene expression patterns in 3D at cellular resolution. Registration algorithms and correlation analysis are then used to compare 3D expression patterns, to automatically detect all statistically significant alterations in mutants, and to map them onto a brain atlas. Automated deep-phenotyping of a mutation in the master transcriptional regulator fezf2 not only detects all known phenotypes but also uncovers important novel neural deficits that were overlooked in previous studies. In the telencephalon, we show for the first time that fezf2 mutant zebrafish have significant patterning deficits, particularly in glutamatergic populations. Our findings reveal unexpected parallels between fezf2 function in zebrafish and mice, where mutations cause deficits in glutamatergic neurons of the telencephalon-derived neocortex. DOI: http://dx.doi.org/10.7554/eLife.23379.001 PMID:28406399

Nuclear Electric Propulsion for Deep Space Exploration

NASA Astrophysics Data System (ADS)

Schmidt, G.

Nuclear electric propulsion (NEP) holds considerable promise for deep space exploration in the future. Research and development of this technology is a key element of NASA's Nuclear Systems Initiative (NSI), which is a top priority in the President's FY03 NASA budget. The goal is to develop the subsystem technologies that will enable application of NEP for missions to the outer planets and beyond by the beginning of next decade. The high-performance offered by nuclear-powered electric thrusters will benefit future missions by (1) reducing or eliminating the launch window constraints associated with complex planetary swingbys, (2) providing the capability to perform large spacecraft velocity changes in deep space, (3) increasing the fraction of vehicle mass allocated to payload and other spacecraft systems, and, (3) in some cases, reducing trip times over other propulsion alternatives. Furthermore, the nuclear energy source will provide a power-rich environment that can support more sophisticated science experiments and higher- speed broadband data transmission than current deep space missions. This paper addresses NASA's plans for NEP, and discusses the subsystem technologies (i.e., nuclear reactors, power conversion and electric thrusters) and system concepts being considered for the first generation of NEP vehicles.

Leukemia and brain tumors in Norwegian railway workers, a nested case-control study.

PubMed

Tynes, T; Jynge, H; Vistnes, A I

1994-04-01

In an attempt to assess whether exposure to electromagnetic fields on Norwegian railways induces brain tumors or leukemia, the authors conducted a nested case-control study of railway workers based on incident cases from the Cancer Registry of Norway in a cohort of 13,030 male Norwegian railway workers who had worked on either electric or non-electric railways. The cohort comprised railway line, outdoor station, and electricity workers. The case series comprised 39 men with brain tumors and 52 men with leukemia (follow-up, 1958-1990). Each case was matched on age with four or five controls selected from the same cohort. The exposure of each study subject to electric and magnetic fields was evaluated from cumulative exposure measures based on present measurements and historical data. Limited information on potential confounders such as creosote, solvents, and herbicides was also collected; information on whether the subject had smoked was obtained by interviews with the subjects or work colleagues. The case-control analysis showed that men employed on electric railways, compared with non-electric ones, had an odds ratio for leukemia of 0.70 (adjusted for smoking) and an odds ratio for brain tumor of 0.87. No significant trend was shown for exposure to either magnetic or electric fields. These results do not support an association between exposure to 16 2/3-Hertz electric or magnetic fields and the risk for leukemia or brain tumors.

Electrical Guidance of Human Stem Cells in the Rat Brain.

PubMed

Feng, Jun-Feng; Liu, Jing; Zhang, Lei; Jiang, Ji-Yao; Russell, Michael; Lyeth, Bruce G; Nolta, Jan A; Zhao, Min

2017-07-11

Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Shielded battery syndrome: a new hardware complication of deep brain stimulation.

PubMed

Chelvarajah, Ramesh; Lumsden, Daniel; Kaminska, Margaret; Samuel, Michael; Hulse, Natasha; Selway, Richard P; Lin, Jean-Pierre; Ashkan, Keyoumars

2012-01-01

Deep brain stimulation hardware is constantly advancing. The last few years have seen the introduction of rechargeable cell technology into the implanted pulse generator design, allowing for longer battery life and fewer replacement operations. The Medtronic® system requires an additional pocket adaptor when revising a non-rechargeable battery such as their Kinetra® to their rechargeable Activa® RC. This additional hardware item can, if it migrates superficially, become an impediment to the recharging of the battery and negate the intended technological advance. To report the emergence of the 'shielded battery syndrome', which has not been previously described. We reviewed our deep brain stimulation database to identify cases of recharging difficulties reported by patients with Activa RC implanted pulse generators. Two cases of shielded battery syndrome were identified. The first required surgery to reposition the adaptor to the deep aspect of the subcutaneous pocket. In the second case, it was possible to perform external manual manipulation to restore the adaptor to its original position deep to the battery. We describe strategies to minimise the occurrence of the shielded battery syndrome and advise vigilance in all patients who experience difficulty with recharging after replacement surgery of this type for the implanted pulse generator. Copyright © 2012 S. Karger AG, Basel.

Targeting the brain: considerations in 332 consecutive patients treated by deep brain stimulation (DBS) for severe neurological diseases.

PubMed

Franzini, Angelo; Cordella, Roberto; Messina, Giuseppe; Marras, Carlo Efisio; Romito, Luigi Michele; Albanese, Alberto; Rizzi, Michele; Nardocci, Nardo; Zorzi, Giovanna; Zekaj, Edvin; Villani, Flavio; Leone, Massimo; Gambini, Orsola; Broggi, Giovanni

2012-12-01

Deep brain stimulation (DBS) extends the treatment of some severe neurological diseases beyond pharmacological and conservative therapy. Our experience extends the field of DBS beyond the treatment of Parkinson disease and dystonia, including several other diseases such as cluster headache and disruptive behavior. Since 1993, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan, 580 deep brain electrodes were implanted in 332 patients. The DBS targets include Stn, GPi, Voa, Vop, Vim, CM-pf, pHyp, cZi, Nacc, IC, PPN, and Brodmann areas 24 and 25. Three hundred patients are still available for follow-up and therapeutic considerations. DBS gave a new therapeutic chance to these patients affected by severe neurological diseases and in some cases controlled life-threatening pathological conditions, which would otherwise result in the death of the patient such as in status dystonicus, status epilepticus and post-stroke hemiballismus. The balance of DBS in severe neurological disease is strongly positive even if further investigations and studies are needed to search for new applications and refine the selection criteria for the actual indications.

Deep learning with convolutional neural networks for EEG decoding and visualization.

PubMed

Schirrmeister, Robin Tibor; Springenberg, Jost Tobias; Fiederer, Lukas Dominique Josef; Glasstetter, Martin; Eggensperger, Katharina; Tangermann, Michael; Hutter, Frank; Burgard, Wolfram; Ball, Tonio

2017-11-01

Deep learning with convolutional neural networks (deep ConvNets) has revolutionized computer vision through end-to-end learning, that is, learning from the raw data. There is increasing interest in using deep ConvNets for end-to-end EEG analysis, but a better understanding of how to design and train ConvNets for end-to-end EEG decoding and how to visualize the informative EEG features the ConvNets learn is still needed. Here, we studied deep ConvNets with a range of different architectures, designed for decoding imagined or executed tasks from raw EEG. Our results show that recent advances from the machine learning field, including batch normalization and exponential linear units, together with a cropped training strategy, boosted the deep ConvNets decoding performance, reaching at least as good performance as the widely used filter bank common spatial patterns (FBCSP) algorithm (mean decoding accuracies 82.1% FBCSP, 84.0% deep ConvNets). While FBCSP is designed to use spectral power modulations, the features used by ConvNets are not fixed a priori. Our novel methods for visualizing the learned features demonstrated that ConvNets indeed learned to use spectral power modulations in the alpha, beta, and high gamma frequencies, and proved useful for spatially mapping the learned features by revealing the topography of the causal contributions of features in different frequency bands to the decoding decision. Our study thus shows how to design and train ConvNets to decode task-related information from the raw EEG without handcrafted features and highlights the potential of deep ConvNets combined with advanced visualization techniques for EEG-based brain mapping. Hum Brain Mapp 38:5391-5420, 2017. © 2017 Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Multimodal Approaches to Define Network Oscillations in Depression

PubMed Central

Smart, Otis Lkuwamy; Tiruvadi, Vineet Ravi; Mayberg, Helen S.

2018-01-01

The renaissance in the use of encephalography-based research methods to probe the pathophysiology of neuropsychiatric disorders is well afoot and continues to advance. Building on the platform of neuroimaging evidence on brain circuit models, magnetoencephalography, scalp electroencephalography, and even invasive electroencephalography are now being used to characterize brain network dysfunctions that underlie major depressive disorder using brain oscillation measurements and associated treatment responses. Such multiple encephalography modalities provide avenues to study pathologic network dynamics with high temporal resolution and over long time courses, opportunities to complement neuroimaging methods and findings, and new approaches to identify quantitative biomarkers that indicate critical targets for brain therapy. Such goals have been facilitated by the ongoing testing of novel invasive neuromodulation therapies, notably, deep brain stimulation, where clinically relevant treatment effects can be monitored at multiple brain sites in a time-locked causal manner. We review key brain rhythms identified in major depressive disorder as foundation for development of putative biomarkers for objectively evaluating neuromodulation success and for guiding deep brain stimulation or other target-based neuromodulation strategies for treatment-resistant depression patients. PMID:25681871

Electrical Stimulation Modulates High γ Activity and Human Memory Performance

PubMed Central

Berry, Brent M.; Miller, Laura R.; Khadjevand, Fatemeh; Ezzyat, Youssef; Wanda, Paul; Sperling, Michael R.; Lega, Bradley; Stead, S. Matt

2018-01-01

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62–118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with “poor” memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation. PMID:29404403

Variable Anisotropic Brain Electrical Conductivities in Epileptogenic Foci

PubMed Central

Mandelkern, M.; Bui, D.; Salamon, N.; Vinters, H. V.; Mathern, G. W.

2010-01-01

Source localization models assume brain electrical conductivities are isotropic at about 0.33 S/m. These assumptions have not been confirmed ex vivo in humans. This study determined bidirectional electrical conductivities from pediatric epilepsy surgery patients. Electrical conductivities perpendicular and parallel to the pial surface of neocortex and subcortical white matter (n = 15) were measured using the 4-electrode technique and compared with clinical variables. Mean (±SD) electrical conductivities were 0.10 ± 0.01 S/m, and varied by 243% from patient to patient. Perpendicular and parallel conductivities differed by 45%, and the larger values were perpendicular to the pial surface in 47% and parallel in 40% of patients. A perpendicular principal axis was associated with normal, while isotropy and parallel principal axes were linked with epileptogenic lesions by MRI. Electrical conductivities were decreased in patients with cortical dysplasia compared with non-dysplasia etiologies. The electrical conductivity values of freshly excised human brain tissues were approximately 30% of assumed values, varied by over 200% from patient to patient, and had erratic anisotropic and isotropic shapes if the MRI showed a lesion. Understanding brain electrical conductivity and ways to non-invasively measure them are probably necessary to enhance the ability to localize EEG sources from epilepsy surgery patients. PMID:20440549

[Stereotactic biopsy in the accurate diagnosis of lesions in the brain stem and deep brain].

PubMed

Qin, F; Huang, Z C; Cai, M Q; Xu, X F; Lu, T T; Dong, Q; Wu, A M; Lu, Z Z; Zhao, C; Guo, Y

2018-06-12

Objective: To investigate the value of stereotactic biopsy in the accurate diagnosis of lesions in the brain stem and deep brain. Methods: A total of 29 consecutive patients who underwent stereotactic biopsy of brainstem and deep brain lesions between May 2012 and January 2018 were retrospectively reviewed. The Cosman-Roberts-Wells (CRW) stereotactic frame was installed under local anesthesia. Thin-layer CT and MRI scanning were performed. Target coordinates were calculated by inputting CT-MRI data into the radionics surgical planning system. The individualized puncture path was designed according to the location of the lesions and the characteristics of the image. Target distributions were as follows: 12 cases of midbrain or pons, 2 cases of internal capsule, 3 cases of thalamus, 12 cases of basal ganglia. The biopsy samples were used for further pathological and/or genetic diagnosis. Results: Twenty-eight of the 29 cases (96.6%) were diagnosed accurately by histopathology and genomic examination following stereotactic biopsy. Pathological results were as follows: 8 cases of lymphoma, 7 cases of glioma, 4 cases of demyelination, 2 cases of germ cell tumor, 2 cases of metastatic tumor, 1 cases of cerebral sparganosis, 1 case of tuberculous granuloma, 1 case of hereditary prion disease, 1 case of glial hyperplasia, 1 case of leukemia. The accurate diagnosis of one case required a combination of histopathology and genomic examination. Undefined diagnosis was still made in 1 cases (3.45%) after biopsy. After biopsy, there were 2 cases (6.9%) with symptomatic slight hemorrhage, 1 case (3.45%) with symptomatic severe hemorrhage, and 1 cass (3.45%) with permanent neurological dysfunction. No one died because of surgery or surgical complications. Conclusions: Stereotactic biopsy is fast, safe and minimally invasive. It is an ideal strategy for accurate diagnosis of lesions in brain stem and deep brain.

An open, multi-vendor, multi-field-strength brain MR dataset and analysis of publicly available skull stripping methods agreement.

PubMed

Souza, Roberto; Lucena, Oeslle; Garrafa, Julia; Gobbi, David; Saluzzi, Marina; Appenzeller, Simone; Rittner, Letícia; Frayne, Richard; Lotufo, Roberto

2018-04-15

This paper presents an open, multi-vendor, multi-field strength magnetic resonance (MR) T1-weighted volumetric brain imaging dataset, named Calgary-Campinas-359 (CC-359). The dataset is composed of images of older healthy adults (29-80 years) acquired on scanners from three vendors (Siemens, Philips and General Electric) at both 1.5 T and 3 T. CC-359 is comprised of 359 datasets, approximately 60 subjects per vendor and magnetic field strength. The dataset is approximately age and gender balanced, subject to the constraints of the available images. It provides consensus brain extraction masks for all volumes generated using supervised classification. Manual segmentation results for twelve randomly selected subjects performed by an expert are also provided. The CC-359 dataset allows investigation of 1) the influences of both vendor and magnetic field strength on quantitative analysis of brain MR; 2) parameter optimization for automatic segmentation methods; and potentially 3) machine learning classifiers with big data, specifically those based on deep learning methods, as these approaches require a large amount of data. To illustrate the utility of this dataset, we compared to the results of a supervised classifier, the results of eight publicly available skull stripping methods and one publicly available consensus algorithm. A linear mixed effects model analysis indicated that vendor (p-value<0.001) and magnetic field strength (p-value<0.001) have statistically significant impacts on skull stripping results. Copyright © 2017 Elsevier Inc. All rights reserved.

Double-blind optimization of subcallosal cingulate deep brain stimulation for treatment-resistant depression: a pilot study.

PubMed

Ramasubbu, Rajamannar; Anderson, Susan; Haffenden, Angela; Chavda, Swati; Kiss, Zelma H T

2013-09-01

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is reported to be a safe and effective new treatment for treatment-resistant depression (TRD). However, the optimal electrical stimulation parameters are unknown and generally selected by trial and error. This pilot study investigated the relationship between stimulus parameters and clinical effects in SCC-DBS treatment for TRD. Four patients with TRD underwent SCC-DBS surgery. In a double-blind stimulus optimization phase, frequency and pulse widths were randomly altered weekly, and corresponding changes in mood and depression were evaluated using a visual analogue scale (VAS) and the 17-item Hamilton Rating Scale for Depression (HAM-D-17). In the open-label postoptimization phase, depressive symptoms were evaluated biweekly for 6 months to determine long-term clinical outcomes. Longer pulse widths (270-450 μs) were associated with reductions in HAM-D-17 scores in 3 patients and maximal happy mood VAS responses in all 4 patients. Only 1 patient showed acute clinical or mood effects from changing the stimulation frequency. After 6 months of open-label therapy, 2 patients responded and 1 patient partially responded. Limitations include small sample size, weekly changes in stimulus parameters, and fixed-order and carry-forward effects. Longer pulse width stimulation may have a role in stimulus optimization for SCC-DBS in TRD. Longer pulse durations produce larger apparent current spread, suggesting that we do not yet know the optimal target or stimulus parameters for this therapy. Investigations using different stimulus parameters are required before embarking on large-scale randomized sham-controlled trials.

Motion illusion – evidence towards human vestibulo-thalamic projections

PubMed Central

Shaikh, Aasef G.; Straumann, Dominik; Palla, Antonella

2017-01-01

Introduction Contemporary studies speculated that cerebellar network responsible for motion perception projects to the cerebral cortex via vestibulo-thalamus. Here we sought for the physiological properties of vestibulo-thalamic pathway responsible for the motion perception. Methods Healthy subjects and the patient with focal vestibulo-thalamic lacunar stroke spun a hand-held rheostat to approximate the value of perceived angular velocity during whole-body passive earth-vertical axis rotations in yaw plane. Vestibulo-ocular reflex was simultaneously measured with high-resolution search coils (paradigm 1). In primates the vestibulo-thalamic projections remain medial and then dorsomedial to the subthalamus. Therefore the paradigm 2 assessed the effects of high-frequency subthalamic nucleus electrical stimulation through the medial and caudal deep brain stimulation electrode in five subjects with Parkinson’s disease. Results Paradigm 1 discovered directional mismatch of perceived rotation in a patient with vestiblo-thalamic lacune. There was no such mismatch in vestibulo-ocular reflex. Healthy subjects did not have such directional discrepancy of perceived motion. The results confirmed that perceived angular motion is relayed through the thalamus. Stimulation through medial and caudal-most electrode of subthalamic deep brain stimulator in paradigm 2 resulted in perception of rotational motion in the horizontal semicircular canal plane. One patient perceived riding a swing, a complex motion, possibly the combination of vertical canal and otolith derived signals representing pitch and fore-aft motion respectively. Conclusion The results examined physiological properties of the vestibulo-thalamic pathway that passes in proximity to the subthalamic nucleus conducting pure semicircular canal signals and convergent signals from the semicircular canals and the otoliths. PMID:28127679

Deep brain stimulation of the ventral hippocampus restores deficits in processing of auditory evoked potentials in a rodent developmental disruption model of schizophrenia.

PubMed

Ewing, Samuel G; Grace, Anthony A

2013-02-01

Existing antipsychotic drugs are most effective at treating the positive symptoms of schizophrenia but their relative efficacy is low and they are associated with considerable side effects. In this study deep brain stimulation of the ventral hippocampus was performed in a rodent model of schizophrenia (MAM-E17) in an attempt to alleviate one set of neurophysiological alterations observed in this disorder. Bipolar stimulating electrodes were fabricated and implanted, bilaterally, into the ventral hippocampus of rats. High frequency stimulation was delivered bilaterally via a custom-made stimulation device and both spectral analysis (power and coherence) of resting state local field potentials and amplitude of auditory evoked potential components during a standard inhibitory gating paradigm were examined. MAM rats exhibited alterations in specific components of the auditory evoked potential in the infralimbic cortex, the core of the nucleus accumbens, mediodorsal thalamic nucleus, and ventral hippocampus in the left hemisphere only. DBS was effective in reversing these evoked deficits in the infralimbic cortex and the mediodorsal thalamic nucleus of MAM-treated rats to levels similar to those observed in control animals. In contrast stimulation did not alter evoked potentials in control rats. No deficits or stimulation-induced alterations were observed in the prelimbic and orbitofrontal cortices, the shell of the nucleus accumbens or ventral tegmental area. These data indicate a normalization of deficits in generating auditory evoked potentials induced by a developmental disruption by acute high frequency, electrical stimulation of the ventral hippocampus. Copyright © 2012 Elsevier B.V. All rights reserved.

Deep brain stimulation of the ventral hippocampus restores deficits in processing of auditory evoked potentials in a rodent developmental disruption model of schizophrenia

PubMed Central

Ewing, Samuel G.; Grace, Anthony A.

2012-01-01

Existing antipsychotic drugs are most effective at treating the positive symptoms of schizophrenia, but their relative efficacy is low and they are associated with considerable side effects. In this study deep brain stimulation of the ventral hippocampus was performed in a rodent model of schizophrenia (MAM-E17) in an attempt to alleviate one set of neurophysiological alterations observed in this disorder. Bipolar stimulating electrodes were fabricated and implanted, bilaterally, into the ventral hippocampus of rats. High frequency stimulation was delivered bilaterally via a custom-made stimulation device and both spectral analysis (power and coherence) of resting state local field potentials and amplitude of auditory evoked potential components during a standard inhibitory gating paradigm were examined. MAM rats exhibited alterations in specific components of the auditory evoked potential in the infralimbic cortex, the core of the nucleus accumbens, mediodorsal thalamic nucleus, and ventral hippocampus in the left hemisphere only. DBS was effective in reversing these evoked deficits in the infralimbic cortex and the mediodorsal thalamic nucleus of MAM-treated rats to levels similar to those observed in control animals. In contrast stimulation did not alter evoked potentials in control rats. No deficits or stimulation-induced alterations were observed in the prelimbic and orbitofrontal cortices, the shell of the nucleus accumbens or ventral tegmental area. These data indicate a normalization of deficits in generating auditory evoked potentials induced by a developmental disruption by acute high frequency, electrical stimulation of the ventral hippocampus. PMID:23269227

Suppression and facilitation of auditory neurons through coordinated acoustic and midbrain stimulation: investigating a deep brain stimulator for tinnitus

NASA Astrophysics Data System (ADS)

Offutt, Sarah J.; Ryan, Kellie J.; Konop, Alexander E.; Lim, Hubert H.

2014-12-01

Objective. The inferior colliculus (IC) is the primary processing center of auditory information in the midbrain and is one site of tinnitus-related activity. One potential option for suppressing the tinnitus percept is through deep brain stimulation via the auditory midbrain implant (AMI), which is designed for hearing restoration and is already being implanted in deaf patients who also have tinnitus. However, to assess the feasibility of AMI stimulation for tinnitus treatment we first need to characterize the functional connectivity within the IC. Previous studies have suggested modulatory projections from the dorsal cortex of the IC (ICD) to the central nucleus of the IC (ICC), though the functional properties of these projections need to be determined. Approach. In this study, we investigated the effects of electrical stimulation of the ICD on acoustic-driven activity within the ICC in ketamine-anesthetized guinea pigs. Main Results. We observed ICD stimulation induces both suppressive and facilitatory changes across ICC that can occur immediately during stimulation and remain after stimulation. Additionally, ICD stimulation paired with broadband noise stimulation at a specific delay can induce greater suppressive than facilitatory effects, especially when stimulating in more rostral and medial ICD locations. Significance. These findings demonstrate that ICD stimulation can induce specific types of plastic changes in ICC activity, which may be relevant for treating tinnitus. By using the AMI with electrode sites positioned with the ICD and the ICC, the modulatory effects of ICD stimulation can be tested directly in tinnitus patients.

Comparison of the Battery Life of Nonrechargeable Generators for Deep Brain Stimulation.

PubMed

Helmers, Ann-Kristin; Lübbing, Isabel; Deuschl, Günther; Witt, Karsten; Synowitz, Michael; Mehdorn, Hubertus Maximilian; Falk, Daniela

2017-11-03

Nonrechargeable deep brain stimulation (DBS) generators must be replaced when the battery capacity is exhausted. Battery life depends on many factors and differs between generator models. A new nonrechargeable generator model replaced the previous model in 2008. Our clinical impression is that the earlier model had a longer battery life than the new one. We conducted this study to substantiate this. We determined the battery life of every DBS generator that had been implanted between 2005 and 2012 in our department for the treatment of Parkinson's disease, and compared the battery lives of the both devices. We calculated the current used by estimating the total electrical energy delivered (TEED) based on the stimulation parameters in use one year after electrode implantation. One hundred ninety-two patients were included in the study; 105 with the old and 86 with the new model generators. The mean battery life in the older model was significantly longer (5.44 ± 0.20 years) than that in the new model (4.44 ± 0.17 years) (p = 0.023). The mean TEED without impedance was 219.9 ± 121.5 mW * Ω in the older model and 145.1 ± 72.7 mW * Ω in the new one, which indicated significantly lower stimulation parameters in the new model (p = 0.00038). The battery life of the new model was significantly shorter than that of the previous model. A lower battery capacity is the most likely reason, since current consumption was similar in both groups. © 2017 International Neuromodulation Society.

Assessment of deep tissue hyperalgesia in the groin - a method comparison of electrical vs. pressure stimulation.

PubMed

Aasvang, E K; Werner, M U; Kehlet, H

2014-09-01

Deep pain complaints are more frequent than cutaneous in post-surgical patients, and a prevalent finding in quantitative sensory testing studies. However, the preferred assessment method - pressure algometry - is indirect and tissue unspecific, hindering advances in treatment and preventive strategies. Thus, there is a need for development of methods with direct stimulation of suspected hyperalgesic tissues to identify the peripheral origin of nociceptive input. We compared the reliability of an ultrasound-guided needle stimulation protocol of electrical detection and pain thresholds to pressure algometry, by performing identical test-retest sequences 10 days apart, in deep tissues in the groin region. Electrical stimulation was performed by five up-and-down staircase series of single impulses of 0.04 ms duration, starting from 0 mA in increments of 0.2 mA until a threshold was reached and descending until sensation was lost. Method reliability was assessed by Bland-Altman plots, descriptive statistics, coefficients of variance and intraclass correlation coefficients. The electrical stimulation method was comparable to pressure algometry regarding 10 days test-retest repeatability, but with superior same-day reliability for electrical stimulation (P < 0.05). Between-subject variance rather than within-subject variance was the main source for test variation. There were no systematic differences in electrical thresholds across tissues and locations (P > 0.05). The presented tissue-specific direct deep tissue electrical stimulation technique has equal or superior reliability compared with the indirect tissue-unspecific stimulation by pressure algometry. This method may facilitate advances in mechanism based preventive and treatment strategies in acute and chronic post-surgical pain states. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation

DTIC Science & Technology

2015-10-01

currently investigating the effects of CG stimulation in subjects with debilitating pain due to cervical or thoracic SCI. This study stemmed from...had a low thoracic injury and pain in lumbar dermatomes, whereas Subject 1 had mainly mid- cervical pain that responded minimally to DBS and matched...AWARD NUMBER: W81XWH-12-1-0559 TITLE: Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation PRINCIPAL

Analysis of EEG activity during sleep - brain hemisphere symmetry of two classes of sleep spindles

NASA Astrophysics Data System (ADS)

Smolen, Magdalena M.

2009-01-01

This paper presents automatic analysis of some selected human electroencephalographic patterns during deep sleep using the Matching Pursuit (MP) algorithm. The periodicity of deep sleep EEG patterns was observed by calculating autocorrelation functions of their percentage contributions. The study confirmed the increasing trend of amplitude-weighted average frequency of sleep spindles from frontal to posterior derivations. The dominant frequencies from the left and the right brain hemisphere were strongly correlated.

Determination of subthalamic nucleus location by quantitative analysis of despiked background neural activity from microelectrode recordings obtained during deep brain stimulation surgery.

PubMed

Danish, Shabbar F; Baltuch, Gordon H; Jaggi, Jurg L; Wong, Stephen

2008-04-01

Microelectrode recording during deep brain stimulation surgery is a useful adjunct for subthalamic nucleus (STN) localization. We hypothesize that information in the nonspike background activity can help identify STN boundaries. We present results from a novel quantitative analysis that accomplishes this goal. Thirteen consecutive microelectrode recordings were retrospectively analyzed. Spikes were removed from the recordings with an automated algorithm. The remaining "despiked" signals were converted via root mean square amplitude and curve length calculations into "feature profile" time series. Subthalamic nucleus boundaries determined by inspection, based on sustained deviations from baseline for each feature profile, were compared against those determined intraoperatively by the clinical neurophysiologist. Feature profile activity within STN exhibited a sustained rise in 10 of 13 tracks (77%). The sensitivity of STN entry was 60% and 90% for curve length and root mean square amplitude, respectively, when agreement within 0.5 mm of the neurophysiologist's prediction was used. Sensitivities were 70% and 100% for 1 mm accuracy. Exit point sensitivities were 80% and 90% for both features within 0.5 mm and 1.0 mm, respectively. Reproducible activity patterns in deep brain stimulation microelectrode recordings can allow accurate identification of STN boundaries. Quantitative analyses of this type may provide useful adjunctive information for electrode placement in deep brain stimulation surgery.

Bimanual Force Coordination in Parkinson’s Disease Patients with Bilateral Subthalamic Deep Brain Stimulation

PubMed Central

Gorniak, Stacey L.; McIntyre, Cameron C.; Alberts, Jay L.

2013-01-01

Objective Studies of bimanual actions similar to activities of daily living (ADLs) are currently lacking in evaluating fine motor control in Parkinson’s disease patients implanted with bilateral subthalamic deep brain stimulators. We investigated basic time and force characteristics of a bimanual task that resembles performance of ADLs in a group of bilateral subthalamic deep brain stimulation (DBS) patients. Methods Patients were evaluated in three different DBS parameter conditions off stimulation, on clinically derived stimulation parameters, and on settings derived from a patient-specific computational model. Model-based parameters were computed as a means to minimize spread of current to non-motor regions of the subthalamic nucleus via Cicerone Deep Brain Stimulation software. Patients were evaluated off parkinsonian medications in each stimulation condition. Results The data indicate that DBS parameter state does not affect most aspects of fine motor control in ADL-like tasks; however, features such as increased grip force and grip symmetry varied with the stimulation state. In the absence of DBS parameters, patients exhibited significant grip force asymmetry. Overall UPDRS-III and UPDRS-III scores associated with hand function were lower while patients were experiencing clinically-derived or model-based parameters, as compared to the off-stimulation condition. Conclusion While bilateral subthalamic DBS has been shown to alleviate gross motor dysfunction, our results indicate that DBS may not provide the same magnitude of benefit to fine motor coordination. PMID:24244388

Neuroprotection for the new millennium. Matchmaking pharmacology and technology

NASA Technical Reports Server (NTRS)

Andrews, R. J.

2001-01-01

A major theme of the 1990s in the pathophysiology of nervous system injury has been the multifactorial etiology of irreversible injury. Multiple causes imply multiple opportunities for therapeutic intervention--hence the abandonment of the "magic bullet" single pharmacologic agent for neuroprotection in favor of pharmacologic "cocktails". A second theme of the 1990s has been the progress in technology for neuroprotection, minimally- or non-invasive monitoring as well as treatment. Cardiac stenting has eliminated the need, in many cases, for open heart surgery; deep brain stimulation for Parkinson's disease has offered significant improvement in quality of life for many who had exhausted cocktail drug treatment for their disease. Deep brain stimulation of the subthalamic nucleus offers a novel treatment for Parkinson's disease where a technological advance may actually be an intervention with effects that are normally expected from pharmacologic agents. Rather than merely "jamming" the nervous system circuits involved in Parkinson's disease, deep brain stimulation of the subthalamic nucleus appears to improve the neurotransmitter imbalance that lies at the heart of Parkinson's disease. It may also slow the progression of the disease. Given the example of deep brain stimulation of the subthalamic nucleus for Parkinson's disease, in future one may expect other technological or "hardware" interventions to influence the programming or "software" of the nervous system's physiologic response in certain disease states.

[High-Definition Exoscope System for Microneurosurgery:Use of an Exoscope in Combination with Tubular Retraction and Frameless Neuronavigation for Microsurgical Resection of Deep Brain Lesions].

PubMed

Nagatani, Kimihiro; Takeuchi, Satoru; Feng, Dongxia; Mori, Kentaro; Day, J Diaz

2015-07-01

The high-definition exoscope (VITOM®, Karl Storz GmbH & Co., Tuttlingen, Germany) is a new equipment that can be used as an alternative to the operating microscope in neurosurgery. Several neurosurgeons have recently reported that the exoscope allows for long working distances and great depth of field. Herein, we review reported cases of exoscope use in neurosurgery. We also describe the advantages of the exoscope compared to the operating microscope and endoscope. Furthermore, we introduce a novel technique for microsurgical resection of deep brain lesions, in which the exoscope is used along with tubular retraction and frameless neuronavigation. Before the operation, neuronavigation is registered and the surgical trajectory is planned to avoid damaging the functional cortex and eloquent white matter tracts. By using intraoperative neuronavigation, the tubular retractor (NICO BrainPath®, NICO Corporation, Indianapolis, US), which is designed to split the white matter when gently inserted, is inserted transcortically into the brain to reach the lesion, along the preplanned trajectory. After insertion, the tubular retractor is fixed in place using a self-retaining arm. This creates a narrow corridor that enables the use of the exoscope (for optimum visualization), bimanual dissection technique, and long bayoneted surgical instruments. The large focal distance of the exoscope allows it to be placed sufficiently further away from the surgical site, permitting the passage of long surgical instruments under the scope. Although obtaining surgical access to deep-seated brain lesions is challenging, we consider that this technique facilitates a safe surgical approach for lesions in deep locations.

Economic substitutability of electrical brain stimulation, food, and water.

PubMed Central

Green, L; Rachlin, H

1991-01-01

Concurrent variable-ratio schedules of electrical brain stimulation, food, and water were paired in various combinations as reinforcement of rats' lever presses. Relative prices of the concurrent reinforcers were varied by changing the ratio of the response requirements on the two levers. Economic substitutability, measured by the sensitivity of response ratio to changes in relative price, was highest with brain stimulation reinforcement of presses on both levers and lowest with food reinforcement of presses on one lever and water reinforcement of presses on the other. Substitutability with brain stimulation reinforcement of presses on one lever and either food or water reinforcement for presses on the other was about as high as with brain stimulation for presses on both levers. Electrical brain stimulation for rats may thus serve as an economic substitute for two reinforcers, neither of which is substitutable for the other. PMID:2037823

Volumetric multimodality neural network for brain tumor segmentation

NASA Astrophysics Data System (ADS)

Silvana Castillo, Laura; Alexandra Daza, Laura; Carlos Rivera, Luis; Arbeláez, Pablo

2017-11-01

Brain lesion segmentation is one of the hardest tasks to be solved in computer vision with an emphasis on the medical field. We present a convolutional neural network that produces a semantic segmentation of brain tumors, capable of processing volumetric data along with information from multiple MRI modalities at the same time. This results in the ability to learn from small training datasets and highly imbalanced data. Our method is based on DeepMedic, the state of the art in brain lesion segmentation. We develop a new architecture with more convolutional layers, organized in three parallel pathways with different input resolution, and additional fully connected layers. We tested our method over the 2015 BraTS Challenge dataset, reaching an average dice coefficient of 84%, while the standard DeepMedic implementation reached 74%.

Network effects of deep brain stimulation

PubMed Central

Alhourani, Ahmad; McDowell, Michael M.; Randazzo, Michael J.; Wozny, Thomas A.; Kondylis, Efstathios D.; Lipski, Witold J.; Beck, Sarah; Karp, Jordan F.; Ghuman, Avniel S.

2015-01-01

The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies. PMID:26269552

Towards deep brain monitoring with superficial EEG sensors plus neuromodulatory focused ultrasound

PubMed Central

Darvas, F; Mehić, E; Caler, CJ; Ojemann, JG; Mourad, PD

2017-01-01

Noninvasive recordings of electrophysiological activity have limited anatomical specificity and depth. We hypothesized that spatially tagging a small volume of brain with a unique electroencephalogram (EEG) signal induced by pulsed focused ultrasound (pFU) could overcome those limitations. As a first step towards testing this hypothesis, we applied transcranial ultrasound (2 MHz, 200 microsecond-long pulses applied at 1050 Hz for one second at a spatial peak temporal average intensity of 1.4 W/cm2) to the brains of anesthetized rats while simultaneously recording EEG signals. We observed a significant 1050 Hz electrophysiological signal only when ultrasound was applied to living brain. Moreover, amplitude demodulation of the EEG signal at 1050 Hz yielded measurement of gamma band (>30 Hz) brain activity consistent with direct measurements of that activity. These results represent preliminary support for use of pFU as a spatial tagging mechanism for non-invasive EEG-based mapping of deep brain activity with high spatial resolution. PMID:27181686

A deep convolutional neural network-based automatic delineation strategy for multiple brain metastases stereotactic radiosurgery.

PubMed

Liu, Yan; Stojadinovic, Strahinja; Hrycushko, Brian; Wardak, Zabi; Lau, Steven; Lu, Weiguo; Yan, Yulong; Jiang, Steve B; Zhen, Xin; Timmerman, Robert; Nedzi, Lucien; Gu, Xuejun

2017-01-01

Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS) treatment planning. In this work, we developed a deep learning convolutional neural network (CNN) algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI) datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS) data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs) of 0.75±0.07 in the tumor core and 0.81±0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67±0.03 and achieved an area under the receiver operating characteristic curve of 0.98±0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases.

Non-invasive measurements of tissue hemodynamics with hybrid diffuse optical methods

NASA Astrophysics Data System (ADS)

Durduran, Turgut

Diffuse optical techniques were used to measure hemodynamics of tissues non-invasively. Spectroscopy and tomography of the brain, muscle and implanted tumors were carried out in animal models and humans. Two qualitatively different methods, diffuse optical tomography and diffuse correlation tomography, were hybridized permitting simultaneous measurement of total hemoglobin concentration, blood oxygen saturation and blood flow. This combination of information was processed further to derive estimates of oxygen metabolism (e.g. CMRO 2) in tissue. The diffuse correlation measurements of blood flow were demonstrated in human tissues, for the first time, demonstrating continous, non-invasive imaging of oxygen metabolism in large tissue volumes several centimeters below the tissue surface. The bulk of these investigations focussed on cerebral hemodynamics. Extensive validation of this methodology was carried out in in vivo rat brain models. Three dimensional images of deep tissue hemodynamics in middle cerebral artery occlusion and cortical spreading depression (CSD) were obtained. CSD hemodynamics were found to depend strongly on partial pressure of carbon dioxide. The technique was then adapted for measurement of human brain. All optical spectroscopic measurements of CMRO2 during functional activation were obtained through intact human skull non-invasively. Finally, a high spatio-temporal resolution measurement of cerebral blood flow due to somatosensory cortex activation following electrical forepaw stimulation in rats was carried out with laser speckle flowmetry. New analysis methods were introduced for laser speckle flowmetry. In other organs, deep tissue hemodynamics were measured on human calf muscle during exercise and cuff-ischemia and were shown to have some clinical utility for peripheral vascular disease. In mice tumor models, the measured hemodynamics were shown to be predictive of photodynamic therapy efficacy, again suggesting promise of clinical utility. In total, the research has pioneered the development of diffuse optical measurements of blood flow, oxygenation and oxygen metabolism in a large range of research and clinical applications.

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens.

PubMed

Ross, Erika K; Kim, Joo Pyung; Settell, Megan L; Han, Seong Rok; Blaha, Charles D; Min, Hoon-Ki; Lee, Kendall H

2016-03-01

Deep brain stimulation (DBS) is a circuit-based treatment shown to relieve symptoms from multiple neurologic and neuropsychiatric disorders. In order to treat the memory deficit associated with Alzheimer's disease (AD), several clinical trials have tested the efficacy of DBS near the fornix. Early results from these studies indicated that patients who received fornix DBS experienced an improvement in memory and quality of life, yet the mechanisms behind this effect remain controversial. It is known that transmission between the medial limbic and corticolimbic circuits plays an integral role in declarative memory, and dysfunction at the circuit level results in various forms of dementia, including AD. Here, we aimed to determine the potential underlying mechanism of fornix DBS by examining the functional circuitry and brain structures engaged by fornix DBS. A multimodal approach was employed to examine global and local temporal changes that occur in an anesthetized swine model of fornix DBS. Changes in global functional activity were measured by functional MRI (fMRI), and local neurochemical changes were monitored by fast scan cyclic voltammetry (FSCV) during electrical stimulation of the fornix. Additionally, intracranial microinfusions into the nucleus accumbens (NAc) were performed to investigate the global activity changes that occur with dopamine and glutamate receptor-specific antagonism. Hemodynamic responses in both medial limbic and corticolimbic circuits measured by fMRI were induced by fornix DBS. Additionally, fornix DBS resulted in increases in dopamine oxidation current (corresponding to dopamine efflux) monitored by FSCV in the NAc. Finally, fornix DBS-evoked hemodynamic responses in the amygdala and hippocampus decreased following dopamine and glutamate receptor antagonism in the NAc. The present findings suggest that fornix DBS modulates dopamine release on presynaptic dopaminergic terminals in the NAc, involving excitatory glutamatergic input, and that the medial limbic and corticolimbic circuits interact in a functional loop. Copyright © 2016 Elsevier Inc. All rights reserved.

The Charging of Composites in the Space Environment

NASA Technical Reports Server (NTRS)

Czepiela, Steven A.

1997-01-01

Deep dielectric charging and subsequent electrostatic discharge in composite materials used on spacecraft have become greater concerns since composite materials are being used more extensively as main structural components. Deep dielectric charging occurs when high energy particles penetrate and deposit themselves in the insulating material of spacecraft components. These deposited particles induce an electric field in the material, which causes the particles to move and thus changes the electric field. The electric field continues to change until a steady state is reached between the incoming particles from the space environment and the particles moving away due to the electric field. An electrostatic discharge occurs when the electric field is greater than the dielectric strength of the composite material. The goal of the current investigation is to investigate deep dielectric charging in composite materials and ascertain what modifications have to be made to the composite properties to alleviate any breakdown issues. A 1-D model was created. The space environment, which is calculated using the Environmental Workbench software, the composite material properties, and the electric field and voltage boundary conditions are input into the model. The output from the model is the charge density, electric field, and voltage distributions as functions of the depth into the material and time. Analysis using the model show that there should be no deep dielectric charging problem with conductive composites such as carbon fiber/epoxy. With insulating materials such as glass fiber/epoxy, Kevlar, and polymers, there is also no concern of deep dielectric charging problems with average day-to-day particle fluxes. However, problems can arise during geomagnetic substorms and solar particle events where particle flux levels increase by several orders of magnitude, and thus increase the electric field in the material by several orders of magnitude. Therefore, the second part of this investigation was an experimental attempt to measure the continuum electrical properties of a carbon fiber/epoxy composite, and to create a composite with tailorable conductivity without affecting its mechanical properties. The measurement of the conductivity and dielectric strength of carbon fiber/epoxy composites showed that these properties are surface layer dominated and difficult to measure. In the second experimental task, the conductivity of a glass fiber/epoxy composite was increased by 3 orders of magnitude, dielectric constant was increased approximately by a factor of 16, with minimal change to the mechanical properties, by adding conductive carbon black to the epoxy.

Investigation of the electric field distribution in the human brain based on MRI and EEG data

NASA Astrophysics Data System (ADS)

Kistenev, Yu. V.; Borisov, A. V.; Knyazkova, A. I.; Shapovalova, A. V.; Ilyasova, E. E.; Sandykova, E. A.

2018-04-01

This work is devoted to the development of the approach to restoration of the spatial-temporal distribution of electric field in the human brain. This field was estimated from the model derived from the Maxwell's equations with boundary conditions corresponding to electric potentials at the EEG electrodes, which are located on the surface of the head according to the standard "10-20" scheme. The MRI data were used for calculation of the spatial distribution of the electrical conductivity of biotissues in the human brain. The study of the electric field distribution using our approach was carried out for the healthy child and the child with autism. The research was carried out using the equipment of the Tomsk Regional Common Use Center of Tomsk State University.

Does processing a shallow and a deep orthography produce different brain activity patterns? An ERP study conducted in Hebrew.

PubMed

Bar-Kochva, Irit

2011-01-01

Orthographies range from shallow orthographies with transparent grapheme-phoneme relations, to deep orthographies, in which these relations are opaque. Two forms of script transcribe the Hebrew language: the shallow pointed script (with diacritics) and the deep unpointed script (without diacritics). This study was set out to examine whether the reading of these scripts evokes distinct brain activity. Preliminary results indicate distinct Event-related-potentials (ERPs). As an equivalent finding was absent when ERPs of non-orthographic stimuli with and without meaningless diacritics were compared, the results imply that print-specific aspects of processing account for the distinct activity elicited by the pointed and unpointed scripts.

VoxResNet: Deep voxelwise residual networks for brain segmentation from 3D MR images.

PubMed

Chen, Hao; Dou, Qi; Yu, Lequan; Qin, Jing; Heng, Pheng-Ann

2018-04-15

Segmentation of key brain tissues from 3D medical images is of great significance for brain disease diagnosis, progression assessment and monitoring of neurologic conditions. While manual segmentation is time-consuming, laborious, and subjective, automated segmentation is quite challenging due to the complicated anatomical environment of brain and the large variations of brain tissues. We propose a novel voxelwise residual network (VoxResNet) with a set of effective training schemes to cope with this challenging problem. The main merit of residual learning is that it can alleviate the degradation problem when training a deep network so that the performance gains achieved by increasing the network depth can be fully leveraged. With this technique, our VoxResNet is built with 25 layers, and hence can generate more representative features to deal with the large variations of brain tissues than its rivals using hand-crafted features or shallower networks. In order to effectively train such a deep network with limited training data for brain segmentation, we seamlessly integrate multi-modality and multi-level contextual information into our network, so that the complementary information of different modalities can be harnessed and features of different scales can be exploited. Furthermore, an auto-context version of the VoxResNet is proposed by combining the low-level image appearance features, implicit shape information, and high-level context together for further improving the segmentation performance. Extensive experiments on the well-known benchmark (i.e., MRBrainS) of brain segmentation from 3D magnetic resonance (MR) images corroborated the efficacy of the proposed VoxResNet. Our method achieved the first place in the challenge out of 37 competitors including several state-of-the-art brain segmentation methods. Our method is inherently general and can be readily applied as a powerful tool to many brain-related studies, where accurate segmentation of brain structures is critical. Copyright © 2017 Elsevier Inc. All rights reserved.

Bayesian convolutional neural network based MRI brain extraction on nonhuman primates.

PubMed

Zhao, Gengyan; Liu, Fang; Oler, Jonathan A; Meyerand, Mary E; Kalin, Ned H; Birn, Rasmus M

2018-07-15

Brain extraction or skull stripping of magnetic resonance images (MRI) is an essential step in neuroimaging studies, the accuracy of which can severely affect subsequent image processing procedures. Current automatic brain extraction methods demonstrate good results on human brains, but are often far from satisfactory on nonhuman primates, which are a necessary part of neuroscience research. To overcome the challenges of brain extraction in nonhuman primates, we propose a fully-automated brain extraction pipeline combining deep Bayesian convolutional neural network (CNN) and fully connected three-dimensional (3D) conditional random field (CRF). The deep Bayesian CNN, Bayesian SegNet, is used as the core segmentation engine. As a probabilistic network, it is not only able to perform accurate high-resolution pixel-wise brain segmentation, but also capable of measuring the model uncertainty by Monte Carlo sampling with dropout in the testing stage. Then, fully connected 3D CRF is used to refine the probability result from Bayesian SegNet in the whole 3D context of the brain volume. The proposed method was evaluated with a manually brain-extracted dataset comprising T1w images of 100 nonhuman primates. Our method outperforms six popular publicly available brain extraction packages and three well-established deep learning based methods with a mean Dice coefficient of 0.985 and a mean average symmetric surface distance of 0.220 mm. A better performance against all the compared methods was verified by statistical tests (all p-values < 10 -4 , two-sided, Bonferroni corrected). The maximum uncertainty of the model on nonhuman primate brain extraction has a mean value of 0.116 across all the 100 subjects. The behavior of the uncertainty was also studied, which shows the uncertainty increases as the training set size decreases, the number of inconsistent labels in the training set increases, or the inconsistency between the training set and the testing set increases. Copyright © 2018 Elsevier Inc. All rights reserved.

High-throughput isotropic mapping of whole mouse brain using multi-view light-sheet microscopy

NASA Astrophysics Data System (ADS)

Nie, Jun; Li, Yusha; Zhao, Fang; Ping, Junyu; Liu, Sa; Yu, Tingting; Zhu, Dan; Fei, Peng

2018-02-01

Light-sheet fluorescence microscopy (LSFM) uses an additional laser-sheet to illuminate selective planes of the sample, thereby enabling three-dimensional imaging at high spatial-temporal resolution. These advantages make LSFM a promising tool for high-quality brain visualization. However, even by the use of LSFM, the spatial resolution remains insufficient to resolve the neural structures across a mesoscale whole mouse brain in three dimensions. At the same time, the thick-tissue scattering prevents a clear observation from the deep of brain. Here we use multi-view LSFM strategy to solve this challenge, surpassing the resolution limit of standard light-sheet microscope under a large field-of-view (FOV). As demonstrated by the imaging of optically-cleared mouse brain labelled with thy1-GFP, we achieve a brain-wide, isotropic cellular resolution of 3μm. Besides the resolution enhancement, multi-view braining imaging can also recover complete signals from deep tissue scattering and attenuation. The identification of long distance neural projections across encephalic regions can be identified and annotated as a result.

DeepNeuron: an open deep learning toolbox for neuron tracing.

PubMed

Zhou, Zhi; Kuo, Hsien-Chi; Peng, Hanchuan; Long, Fuhui

2018-06-06

Reconstructing three-dimensional (3D) morphology of neurons is essential for understanding brain structures and functions. Over the past decades, a number of neuron tracing tools including manual, semiautomatic, and fully automatic approaches have been developed to extract and analyze 3D neuronal structures. Nevertheless, most of them were developed based on coding certain rules to extract and connect structural components of a neuron, showing limited performance on complicated neuron morphology. Recently, deep learning outperforms many other machine learning methods in a wide range of image analysis and computer vision tasks. Here we developed a new Open Source toolbox, DeepNeuron, which uses deep learning networks to learn features and rules from data and trace neuron morphology in light microscopy images. DeepNeuron provides a family of modules to solve basic yet challenging problems in neuron tracing. These problems include but not limited to: (1) detecting neuron signal under different image conditions, (2) connecting neuronal signals into tree(s), (3) pruning and refining tree morphology, (4) quantifying the quality of morphology, and (5) classifying dendrites and axons in real time. We have tested DeepNeuron using light microscopy images including bright-field and confocal images of human and mouse brain, on which DeepNeuron demonstrates robustness and accuracy in neuron tracing.

The seizure, not electricity, is essential in convulsive therapy: the flurothyl experience.

PubMed

Fink, Max

2014-06-01

For more than 50 years, research in convulsive therapy has been focused on the impact of electricity and seizures on memory and not on brain chemistry or neurophysiology. Brief pulse and ultra-brief pulse currents replaced sinusoidal currents. Electrode placements were varied, energy dosing was altered, and electricity was replaced by magnetic currents. The published experiences and archival records of seizures induced by camphor, pentylenetetrazol, and flurothyl are reviewed and compared with the changes induced by electricity. The clinical efficacy of chemically induced seizures is equal to that of electrical inductions. Seizure durations are longer, and impairment of cognition and memory is less. Electroconvulsive therapy replaced chemical treatments for ease of use, not for greater efficacy or safety. The brain seizure, not the method of induction, is the essential element in the efficacy of convulsive therapy. Seizure induction with chemicals avoids the direct effects of electricity on brain functions with lesser effects on cognition. Reexamination of chemical inductions of seizures as replacements for electricity is encouraged.

A Deep Learning Approach to Neuroanatomical Characterisation of Alzheimer's Disease.

PubMed

Ambastha, Abhinit Kumar; Leong, Tze-Yun

2017-01-01

Alzheimer's disease (AD) is a neurological degenerative disorder that leads to progressive mental deterioration. This work introduces a computational approach to improve our understanding of the progression of AD. We use ensemble learning methods and deep neural networks to identify salient structural correlations among brain regions that degenerate together in AD; this provides an understanding of how AD progresses in the brain. The proposed technique has a classification accuracy of 81.79% for AD against healthy subjects using a single modality imaging dataset.

The Role of a Neuropsychologist on a Movement Disorders Deep Brain Stimulation Team.

PubMed

Kubu, Cynthia S

2018-05-01

The term movement disorders is misleading in the implication that the symptoms are limited to motor problems. Most movement disorders include a variety of neurobehavioral and neurocognitive symptoms that require neuropsychological expertise. The goal of this paper is to provide a rationale and practical roadmap for neuropsychologists' involvement in a Movement Disorders team with a specific focus on pre-operative deep brain stimulation (DBS) evaluations. Pragmatic recommendations regarding requisite skills, clinical practice, recommendations, communication, and benefits are outlined.

Deep learning for brain tumor classification

NASA Astrophysics Data System (ADS)

Paul, Justin S.; Plassard, Andrew J.; Landman, Bennett A.; Fabbri, Daniel

2017-03-01

Recent research has shown that deep learning methods have performed well on supervised machine learning, image classification tasks. The purpose of this study is to apply deep learning methods to classify brain images with different tumor types: meningioma, glioma, and pituitary. A dataset was publicly released containing 3,064 T1-weighted contrast enhanced MRI (CE-MRI) brain images from 233 patients with either meningioma, glioma, or pituitary tumors split across axial, coronal, or sagittal planes. This research focuses on the 989 axial images from 191 patients in order to avoid confusing the neural networks with three different planes containing the same diagnosis. Two types of neural networks were used in classification: fully connected and convolutional neural networks. Within these two categories, further tests were computed via the augmentation of the original 512×512 axial images. Training neural networks over the axial data has proven to be accurate in its classifications with an average five-fold cross validation of 91.43% on the best trained neural network. This result demonstrates that a more general method (i.e. deep learning) can outperform specialized methods that require image dilation and ring-forming subregions on tumors.

Electrical stimulation site influences the spatial distribution of motor units recruited in tibialis anterior.

PubMed

Okuma, Yoshino; Bergquist, Austin J; Hong, Mandy; Chan, K Ming; Collins, David F

2013-11-01

To compare the spatial distribution of motor units recruited in tibialis anterior (TA) when electrical stimulation is applied over the TA muscle belly versus the common peroneal nerve trunk. Electromyography (EMG) was recorded from the surface and from fine wires in superficial and deep regions of TA. Separate M-wave recruitment curves were constructed for muscle belly and nerve trunk stimulation. During muscle belly stimulation, significantly more current was required to generate M-waves that were 5% of the maximal M-wave (M max; M5%max), 50% M max (M 50%max) and 95% M max (M 95%max) at the deep versus the superficial recording site. In contrast, during nerve trunk stimulation, there were no differences in the current required to reach M5%max, M 50%max or M 95%max between deep and superficial recording sites. Surface EMG reflected activity in both superficial and deep muscle regions. Stimulation over the muscle belly recruited motor units from superficial to deep with increasing stimulation amplitude. Stimulation over the nerve trunk recruited superficial and deep motor units equally, regardless of stimulation amplitude. These results support the idea that where electrical stimulation is applied markedly affects how contractions are produced and have implications for the interpretation of surface EMG data. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

MEG Can Map Short and Long-Term Changes in Brain Activity following Deep Brain Stimulation for Chronic Pain

PubMed Central

Mohseni, Hamid R.; Smith, Penny P.; Parsons, Christine E.; Young, Katherine S.; Hyam, Jonathan A.; Stein, Alan; Stein, John F.; Green, Alexander L.; Aziz, Tipu Z.; Kringelbach, Morten L.

2012-01-01

Deep brain stimulation (DBS) has been shown to be clinically effective for some forms of treatment-resistant chronic pain, but the precise mechanisms of action are not well understood. Here, we present an analysis of magnetoencephalography (MEG) data from a patient with whole-body chronic pain, in order to investigate changes in neural activity induced by DBS for pain relief over both short- and long-term. This patient is one of the few cases treated using DBS of the anterior cingulate cortex (ACC). We demonstrate that a novel method, null-beamforming, can be used to localise accurately brain activity despite the artefacts caused by the presence of DBS electrodes and stimulus pulses. The accuracy of our source localisation was verified by correlating the predicted DBS electrode positions with their actual positions. Using this beamforming method, we examined changes in whole-brain activity comparing pain relief achieved with deep brain stimulation (DBS ON) and compared with pain experienced with no stimulation (DBS OFF). We found significant changes in activity in pain-related regions including the pre-supplementary motor area, brainstem (periaqueductal gray) and dissociable parts of caudal and rostral ACC. In particular, when the patient reported experiencing pain, there was increased activity in different regions of ACC compared to when he experienced pain relief. We were also able to demonstrate long-term functional brain changes as a result of continuous DBS over one year, leading to specific changes in the activity in dissociable regions of caudal and rostral ACC. These results broaden our understanding of the underlying mechanisms of DBS in the human brain. PMID:22675503

White Matter Hyperintensities Are Under Strong Genetic Influence.

PubMed

Sachdev, Perminder S; Thalamuthu, Anbupalam; Mather, Karen A; Ames, David; Wright, Margaret J; Wen, Wei

2016-06-01

The genetic basis of white matter hyperintensities (WMH) is still unknown. This study examines the heritability of WMH in both sexes and in different brain regions, and the influence of age. Participants from the Older Australian Twins Study were recruited (n=320; 92 monozygotic and 68 dizygotic pairs) who volunteered for magnetic resonance imaging scans and medical assessments. Heritability, that is, the ratio of the additive genetic variance to the total phenotypic variance, was estimated using the twin design. Heritability was high for total WMH volume (0.76), and for periventricular WMH (0.64) and deep WMH (0.77), and varied from 0.18 for the cerebellum to 0.76 for the occipital lobe. The genetic correlation between deep and periventricular WMH regions was 0.85, with one additive genetics factor accounting for most of the shared variance. Heritability was consistently higher in women in the cerebral regions. Heritability in deep but not periventricular WMH declined with age, in particular after the age of 75. WMH have a strong genetic influence but this is not uniform through the brain, being higher for deep than periventricular WMH and in the cerebral regions. The genetic influence is higher in women, and there is an age-related decline, most markedly for deep WMH. The data suggest some heterogeneity in the pathogenesis of WMH for different brain regions and for men and women. © 2016 American Heart Association, Inc.

New MR imaging assessment tool to define brain abnormalities in very preterm infants at term.

PubMed

Kidokoro, H; Neil, J J; Inder, T E

2013-01-01

WM injury is the dominant form of injury in preterm infants. However, other cerebral structures, including the deep gray matter and the cerebellum, can also be affected by injury and/or impaired growth. Current MR imaging injury assessment scales are subjective and are challenging to apply. Thus, we developed a new assessment tool and applied it to MR imaging studies obtained from very preterm infants at term age. MR imaging scans from 97 very preterm infants (< 30 weeks' gestation) and 22 healthy term-born infants were evaluated retrospectively. The severity of brain injury (defined by signal abnormalities) and impaired brain growth (defined with biometrics) was scored in the WM, cortical gray matter, deep gray matter, and cerebellum. Perinatal variables for clinical risks were collected. In very preterm infants, brain injury was observed in the WM (n=23), deep GM (n=5), and cerebellum (n=23). Combining measures of injury and impaired growth showed moderate to severe abnormalities most commonly in the WM (n=38) and cerebellum (n=32) but still notable in the cortical gray matter (n=16) and deep gray matter (n=11). WM signal abnormalities were associated with a reduced deep gray matter area but not with cerebellar abnormality. Intraventricular and/or parenchymal hemorrhage was associated with cerebellar signal abnormality and volume reduction. Multiple clinical risk factors, including prolonged intubation, prolonged parenteral nutrition, postnatal corticosteroid use, and postnatal sepsis, were associated with increased global abnormality on MR imaging. Very preterm infants demonstrate a high prevalence of injury and growth impairment in both the WM and gray matter. This MR imaging scoring system provides a more comprehensive and objective classification of the nature and extent of abnormalities than existing measures.

Electrical stimulation of acupoint combinations against deep venous thrombosis in elderly bedridden patients after major surgery.

PubMed

Hou, Lili; Chen, Cuiping; Xu, Lei; Yin, Peihao; Peng, Wen

2013-04-01

To compare the effects of electrical stimulation of different acupoint combinations among postoperative bedridden elderly patients on hemorheology and deep venous blood flow velocity and investigate the.role of electrical stimulation against deep vein thrombosis (DVT). From November 2010 to October 2011, a total of 160 elderly bedridden patients after major surgery were divided into the conventional care group, invigorating and promoting Qi group, blood-activating and damp-eliminating group, and acupoint-combination stimulation group. Whole blood viscosity, plasma viscosity, D-dimer levels, lower limb skin temperature, lower limb circumference, and flow velocities of the external iliac vein, femoral vein, popliteal vein, and deep calf veins in all patients were documented and compared among the four groups. Whole blood viscosity, plasma viscosity, D-dimer levels, and lower limb circumference were significantly reduced in the blood-activating and damp-eliminating group compared with the conventional care group (P < 0.05) and were almost equal to those in the acupoint-combination stimulation group (P > 0.05). Lower limb venous flow velocities were accelerated in the invigorating and promoting Qi group compared with the other groups, excluding the acupoint-combination stimulation group (P < 0.05). Hemorheological indices in postoperative bedridden elderly patients were improved after combined electrical stimulation at Yinlingquan (SP 9) and Sanyinjiao (SP 6). Combined electrical stimulation at Zusanli (ST 36) and Taichong (LR 3), on the other hand, accelerated lower limb venous flow.

The Brain Rotation and Brain Diffusion Strategies of Small Islanders: Considering "Movement" in Lieu of "Place"

ERIC Educational Resources Information Center

Baldacchino, Godfrey

2006-01-01

The "brain drain" phenomenon is typically seen as a zero-sum game, where one party's gain is presumed to be another's drain. This corresponds to deep-seated assumptions about what is "home" and what is "away". This article challenges the view, driven by much "brain drain" literature, that the dynamic is an…

Neuromechanism Study of Insect–Machine Interface: Flight Control by Neural Electrical Stimulation

PubMed Central

Zhao, Huixia; Zheng, Nenggan; Ribi, Willi A.; Zheng, Huoqing; Xue, Lei; Gong, Fan; Zheng, Xiaoxiang; Hu, Fuliang

2014-01-01

The insect–machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee–machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control. PMID:25409523

Neuromechanism study of insect-machine interface: flight control by neural electrical stimulation.

PubMed

Zhao, Huixia; Zheng, Nenggan; Ribi, Willi A; Zheng, Huoqing; Xue, Lei; Gong, Fan; Zheng, Xiaoxiang; Hu, Fuliang

2014-01-01

The insect-machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee-machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control.

Deep Brain Stimulation for Parkinson's Disease

MedlinePlus

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Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease

PubMed Central

de Hemptinne, Coralie; Swann, Nicole; Ostrem, Jill L.; Ryapolova-Webb, Elena S.; Luciano, Marta San; Galifianakis, Nicholas; Starr, Philip A.

2015-01-01

Deep brain stimulation (DBS) is increasingly applied to the treatment of brain disorders, but its mechanism of action remains unknown. Here, we evaluate the effect of basal ganglia DBS on cortical function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the β rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive β phase locking of motor cortex neurons. PMID:25867121

A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease.

PubMed

Bardinet, Eric; Bhattacharjee, Manik; Dormont, Didier; Pidoux, Bernard; Malandain, Grégoire; Schüpbach, Michael; Ayache, Nicholas; Cornu, Philippe; Agid, Yves; Yelnik, Jérôme

2009-02-01

The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

A deep learning model integrating FCNNs and CRFs for brain tumor segmentation.

PubMed

Zhao, Xiaomei; Wu, Yihong; Song, Guidong; Li, Zhenye; Zhang, Yazhuo; Fan, Yong

2018-01-01

Accurate and reliable brain tumor segmentation is a critical component in cancer diagnosis, treatment planning, and treatment outcome evaluation. Build upon successful deep learning techniques, a novel brain tumor segmentation method is developed by integrating fully convolutional neural networks (FCNNs) and Conditional Random Fields (CRFs) in a unified framework to obtain segmentation results with appearance and spatial consistency. We train a deep learning based segmentation model using 2D image patches and image slices in following steps: 1) training FCNNs using image patches; 2) training CRFs as Recurrent Neural Networks (CRF-RNN) using image slices with parameters of FCNNs fixed; and 3) fine-tuning the FCNNs and the CRF-RNN using image slices. Particularly, we train 3 segmentation models using 2D image patches and slices obtained in axial, coronal and sagittal views respectively, and combine them to segment brain tumors using a voting based fusion strategy. Our method could segment brain images slice-by-slice, much faster than those based on image patches. We have evaluated our method based on imaging data provided by the Multimodal Brain Tumor Image Segmentation Challenge (BRATS) 2013, BRATS 2015 and BRATS 2016. The experimental results have demonstrated that our method could build a segmentation model with Flair, T1c, and T2 scans and achieve competitive performance as those built with Flair, T1, T1c, and T2 scans. Copyright © 2017 Elsevier B.V. All rights reserved.

Tourette syndrome and other chronic tic disorders: an update on clinical management.

PubMed

Martino, Davide; Pringsheim, Tamara M

2018-02-01

The management of Tourette syndrome (TS) and other chronic tic disorders occurs in multiple stages and begins with comprehensive assessment and complex psychoeducation. Behavioral and pharmacological interventions (second stage) are needed when tics cause physical or psychosocial impairment. Deep brain stimulation surgery or experimental therapies represent the third stage. Areas covered: Discussed are recent advances in assessment and therapy of chronic tic disorders, encompassing the three stages of intervention, with the addition of experimental, non-invasive brain stimulation strategies. A PubMed search was performed using as keywords: 'tic disorders', 'Tourette syndrome', 'assessment', 'rating scales', 'behavioral treatment', 'pharmacological treatment', 'deep brain stimulation', 'transcranial magnetic (or current) stimulation', and 'transcranial current stimulation'. More than 300 peer-reviewed articles were evaluated. The studies discussed have been selected on the basis of novelty and impact. Expert commentary: Comprehensive assessment of tic disorders and psychoeducation are crucial to a correct active management approach. Behavioral treatments represent first line of active interventions, with increasing potential offered by telehealth. Antipsychotics and alpha agonists remain first line pharmacological interventions for tics, although VMAT-2 inhibitors appear promising. Deep brain stimulation is a potential option for medically refractory, severely disabled patients with tics, but age and target selection require further investigation.

Deep brain optical measurements of cell type-specific neural activity in behaving mice.

PubMed

Cui, Guohong; Jun, Sang Beom; Jin, Xin; Luo, Guoxiang; Pham, Michael D; Lovinger, David M; Vogel, Steven S; Costa, Rui M

2014-01-01

Recent advances in genetically encoded fluorescent sensors enable the monitoring of cellular events from genetically defined groups of neurons in vivo. In this protocol, we describe how to use a time-correlated single-photon counting (TCSPC)-based fiber optics system to measure the intensity, emission spectra and lifetime of fluorescent biosensors expressed in deep brain structures in freely moving mice. When combined with Cre-dependent selective expression of genetically encoded Ca(2+) indicators (GECIs), this system can be used to measure the average neural activity from a specific population of cells in mice performing complex behavioral tasks. As an example, we used viral expression of GCaMPs in striatal projection neurons (SPNs) and recorded the fluorescence changes associated with calcium spikes from mice performing a lever-pressing operant task. The whole procedure, consisting of virus injection, behavior training and optical recording, takes 3-4 weeks to complete. With minor adaptations, this protocol can also be applied to recording cellular events from other cell types in deep brain regions, such as dopaminergic neurons in the ventral tegmental area. The simultaneously recorded fluorescence signals and behavior events can be used to explore the relationship between the neural activity of specific brain circuits and behavior.

Deep brain stimulation for the treatment of uncommon tremor syndromes.

PubMed

Ramirez-Zamora, Adolfo; Okun, Michael S

2016-08-01

Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson's disease however the effectiveness and long-term outcomes of DBS in other uncommon and complex tremor syndromes has not been well established. Traditionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered the main target for medically intractable tremors; however alternative brain regions and improvements in stereotactic techniques and hardware may soon change the horizon for treatment of complex tremors. In this article, we conducted a PubMed search using different combinations between the terms 'Uncommon tremors', 'Dystonic tremor', 'Holmes tremor' 'Midbrain tremor', 'Rubral tremor', 'Cerebellar tremor', 'outflow tremor', 'Multiple Sclerosis tremor', 'Post-traumatic tremor', 'Neuropathic tremor', and 'Deep Brain Stimulation/DBS'. Additionally, we examined and summarized the current state of evolving interventions for treatment of complex tremor syndromes. Expert commentary: Recently reported interventions for rare tremors include stimulation of the posterior subthalamic area, globus pallidus internus, ventralis oralis anterior/posterior thalamic subnuclei, and the use of dual lead stimulation in one or more of these targets. Treatment should be individualized and dictated by tremor phenomenology and associated clinical features.

Dynamics of scene representations in the human brain revealed by magnetoencephalography and deep neural networks

PubMed Central

Cichy, Radoslaw Martin; Khosla, Aditya; Pantazis, Dimitrios; Oliva, Aude

2017-01-01

Human scene recognition is a rapid multistep process evolving over time from single scene image to spatial layout processing. We used multivariate pattern analyses on magnetoencephalography (MEG) data to unravel the time course of this cortical process. Following an early signal for lower-level visual analysis of single scenes at ~100 ms, we found a marker of real-world scene size, i.e. spatial layout processing, at ~250 ms indexing neural representations robust to changes in unrelated scene properties and viewing conditions. For a quantitative model of how scene size representations may arise in the brain, we compared MEG data to a deep neural network model trained on scene classification. Representations of scene size emerged intrinsically in the model, and resolved emerging neural scene size representation. Together our data provide a first description of an electrophysiological signal for layout processing in humans, and suggest that deep neural networks are a promising framework to investigate how spatial layout representations emerge in the human brain. PMID:27039703

Deep Brain Stimulation of the Memory Circuit: Improving Cognition in Alzheimer's Disease.

PubMed

Posporelis, Sotirios; David, Anthony S; Ashkan, Keyoumars; Shotbolt, Paul

2018-05-26

Deep brain stimulation (DBS) is an effective invasive treatment for a wide range of neurological and psychiatric disorders. Neurosurgically implanted electrodes deliver stimulation of pre-programmed amplitude, frequency, and pulse width within deep brain structures; those settings can be adjusted at a later stage according to individual needs for optimal response. This results in variable effects dependent on the targeted region. An established treatment for movement disorders, the effectiveness of DBS in dementia remains under investigation. Translational studies have uncovered a pro-cognitive effect mediated by changes on cellular as well as network level. Several groups have attempted to examine the benefits of DBS in Alzheimer's disease; differences in inclusion criteria and methodology make generalization of results difficult. This review aims to summarize all completed and ongoing human studies of DBS in Alzheimer's disease. The results are classified by targeted anatomical structure. Future directions, as well as economical and ethical arguments, are explored in the final section.

Generation and evaluation of an ultra-high-field atlas with applications in DBS planning

NASA Astrophysics Data System (ADS)

Wang, Brian T.; Poirier, Stefan; Guo, Ting; Parrent, Andrew G.; Peters, Terry M.; Khan, Ali R.

2016-03-01

Purpose Deep brain stimulation (DBS) is a common treatment for Parkinson's disease (PD) and involves the use of brain atlases or intrinsic landmarks to estimate the location of target deep brain structures, such as the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi). However, these structures can be difficult to localize with conventional clinical magnetic resonance imaging (MRI), and thus targeting can be prone to error. Ultra-high-field imaging at 7T has the ability to clearly resolve these structures and thus atlases built with these data have the potential to improve targeting accuracy. Methods T1 and T2-weighted images of 12 healthy control subjects were acquired using a 7T MR scanner. These images were then used with groupwise registration to generate an unbiased average template with T1w and T2w contrast. Deep brain structures were manually labelled in each subject by two raters and rater reliability was assessed. We compared the use of this unbiased atlas with two other methods of atlas-based segmentation (single-template and multi-template) for subthalamic nucleus (STN) segmentation on 7T MRI data. We also applied this atlas to clinical DBS data acquired at 1.5T to evaluate its efficacy for DBS target localization as compared to using a standard atlas. Results The unbiased templates provide superb detail of subcortical structures. Through one-way ANOVA tests, the unbiased template is significantly (p <0.05) more accurate than a single-template in atlas-based segmentation and DBS target localization tasks. Conclusion The generated unbiased averaged templates provide better visualization of deep brain nuclei and an increase in accuracy over single-template and lower field strength atlases.

Electromagnetic interference of GSM mobile phones with the implantable deep brain stimulator, ITREL-III

PubMed Central

Kainz, Wolfgang; Alesch, François; Chan, Dulciana Dias

2003-01-01

Background The purpose was to investigate mobile phone interference with implantable deep brain stimulators by means of 10 different 900 Mega Hertz (MHz) and 10 different 1800 MHz GSM (Global System for Mobile Communications) mobile phones. Methods All tests were performed in vitro using a phantom especially developed for testing with deep brain stimulators. The phantom was filled with liquid phantom materials simulating brain and muscle tissue. All examinations were carried out inside an anechoic chamber on two implants of the same type of deep brain stimulator: ITREL-III from Medtronic Inc., USA. Results Despite a maximum transmitted peak power of mobile phones of 1 Watt (W) at 1800 MHz and 2 W at 900 MHz respectively, no influence on the ITREL-III was found. Neither the shape of the pulse form changed nor did single pulses fail. Tests with increased transmitted power using CW signals and broadband dipoles have shown that inhibition of the ITREL-III occurs at frequency dependent power levels which are below the emissions of GSM mobile phones. The ITREL-III is essentially more sensitive at 1800 MHz than at 900 MHz. Particularly the frequency range around 1500 MHz shows a very low interference threshold. Conclusion These investigations do not indicate a direct risk for ITREL-III patients using the tested GSM phones. Based on the interference levels found with CW signals, which are below the mobile phone emissions, we recommend similar precautions as for patients with cardiac pacemakers: 1. The phone should be used at the ear at the opposite side of the implant and 2. The patient should avoid carrying the phone close to the implant. PMID:12773204

Use of brain electrical activity for the identification of hematomas in mild traumatic brain injury.

PubMed

Hanley, Daniel F; Chabot, Robert; Mould, W Andrew; Morgan, Timothy; Naunheim, Rosanne; Sheth, Kevin N; Chiang, William; Prichep, Leslie S

2013-12-15

This study investigates the potential clinical utility in the emergency department (ED) of an index of brain electrical activity to identify intracranial hematomas. The relationship between this index and depth, size, and type of hematoma was explored. Ten minutes of brain electrical activity was recorded from a limited montage in 38 adult patients with traumatic hematomas (CT scan positive) and 38 mild head injured controls (CT scan negative) in the ED. The volume of blood and distance from recording electrodes were measured by blinded independent experts. Brain electrical activity data were submitted to a classification algorithm independently developed traumatic brain injury (TBI) index to identify the probability of a CT+traumatic event. There was no significant relationship between the TBI-Index and type of hematoma, or distance of the bleed from recording sites. A significant correlation was found between TBI-Index and blood volume. The sensitivity to hematomas was 100%, positive predictive value was 74.5%, and positive likelihood ratio was 2.92. The TBI-Index, derived from brain electrical activity, demonstrates high accuracy for identification of traumatic hematomas. Further, this was not influenced by distance of the bleed from the recording electrodes, blood volume, or type of hematoma. Distance and volume limitations noted with other methods, (such as that based on near-infrared spectroscopy) were not found, thus suggesting the TBI-Index to be a potentially important adjunct to acute assessment of head injury. Because of the life-threatening risk of undetected hematomas (false negatives), specificity was permitted to be lower, 66%, in exchange for extremely high sensitivity.

Development of precise measurement systems for deep-sea electrical and magnetic explorations by ROV and AUV

NASA Astrophysics Data System (ADS)

Sayanagi, K.; Goto, T.; Harada, M.; Kasaya, T.; Sawa, T.; Nakajima, T.; Isezaki, N.; Takeuchi, A.; Nagao, T.; Matsuo, J.

2009-12-01

It is generally not easy to obtain the fine-scale structure of the oceanic crust with accuracy better than several tens of meters, because the deep sea prevents us from approaching the bottom in most parts of the oceans. The necessity of such detailed information, however, has increased in researches and developments of the ocean floor. For instance, it is essential in development of ocean floor resources like sea-floor hydrothermal deposits and methane hydrate in order to estimate accurate abundance of those resources. Therefore, it is very important to develop some instruments for precise measurements of the oceanic crust. From this standpoint, we have developed new measurement systems for electrical and magnetic explorations by Remotely Operated Vehicle (ROV) and Autonomous Underwater Vehicle (AUV). In our project, the main target is sea-floor hydrothermal deposits. We are working on research and development regarding measurement of the magnetic field with high resolution and high sampling rate, electrical exploration with accurately controlled source signals, electrical exploration tools for shallow and deep targets, versatile instruments of electrical and magnetic explorations with multi-platforms (deep-tow system, ROV, and AUV), comprehensive analyses of electrical, magnetic, acoustic and thermal data, and so on. We finished basic designs of the magnetic and electrical observation systems last year, and we have been manufacturing each instrument. So far, the first test of the magnetic exploration system was carried out in the Kumano Basin during the R/V Yokosuka cruise in July, 2009. In the test, a vector magnetometer on AUV “Urashima” and a scalar magnetometer hung below towing vehicle “Yokosuka Deep-Tow” successfully detected magnetic anomaly produced by an artificial magnetic body set up on the ocean floor. Details will be reported in another paper by Harada, M. et al. in this meeting. In addition, various performance tests will be planned for check and improvement of the observation systems. For instance, the vector magnetometer will be tested over a volcanic island using a helicopter. The electrical exploration system will be also tested using ROV “Kaiko 7000II” off the northeastern part of Japan during the R/V Kairei cruise. We will present the outline and the current state of the project in this presentation. Note that this project has been supported by the Ministry of Education, Culture, Sports, Science & Technology (MEXT).

Deep ensemble learning of sparse regression models for brain disease diagnosis.

PubMed

Suk, Heung-Il; Lee, Seong-Whan; Shen, Dinggang

2017-04-01

Recent studies on brain imaging analysis witnessed the core roles of machine learning techniques in computer-assisted intervention for brain disease diagnosis. Of various machine-learning techniques, sparse regression models have proved their effectiveness in handling high-dimensional data but with a small number of training samples, especially in medical problems. In the meantime, deep learning methods have been making great successes by outperforming the state-of-the-art performances in various applications. In this paper, we propose a novel framework that combines the two conceptually different methods of sparse regression and deep learning for Alzheimer's disease/mild cognitive impairment diagnosis and prognosis. Specifically, we first train multiple sparse regression models, each of which is trained with different values of a regularization control parameter. Thus, our multiple sparse regression models potentially select different feature subsets from the original feature set; thereby they have different powers to predict the response values, i.e., clinical label and clinical scores in our work. By regarding the response values from our sparse regression models as target-level representations, we then build a deep convolutional neural network for clinical decision making, which thus we call 'Deep Ensemble Sparse Regression Network.' To our best knowledge, this is the first work that combines sparse regression models with deep neural network. In our experiments with the ADNI cohort, we validated the effectiveness of the proposed method by achieving the highest diagnostic accuracies in three classification tasks. We also rigorously analyzed our results and compared with the previous studies on the ADNI cohort in the literature. Copyright © 2017 Elsevier B.V. All rights reserved.

Deep ensemble learning of sparse regression models for brain disease diagnosis

PubMed Central

Suk, Heung-Il; Lee, Seong-Whan; Shen, Dinggang

2018-01-01

Recent studies on brain imaging analysis witnessed the core roles of machine learning techniques in computer-assisted intervention for brain disease diagnosis. Of various machine-learning techniques, sparse regression models have proved their effectiveness in handling high-dimensional data but with a small number of training samples, especially in medical problems. In the meantime, deep learning methods have been making great successes by outperforming the state-of-the-art performances in various applications. In this paper, we propose a novel framework that combines the two conceptually different methods of sparse regression and deep learning for Alzheimer’s disease/mild cognitive impairment diagnosis and prognosis. Specifically, we first train multiple sparse regression models, each of which is trained with different values of a regularization control parameter. Thus, our multiple sparse regression models potentially select different feature subsets from the original feature set; thereby they have different powers to predict the response values, i.e., clinical label and clinical scores in our work. By regarding the response values from our sparse regression models as target-level representations, we then build a deep convolutional neural network for clinical decision making, which thus we call ‘ Deep Ensemble Sparse Regression Network.’ To our best knowledge, this is the first work that combines sparse regression models with deep neural network. In our experiments with the ADNI cohort, we validated the effectiveness of the proposed method by achieving the highest diagnostic accuracies in three classification tasks. We also rigorously analyzed our results and compared with the previous studies on the ADNI cohort in the literature. PMID:28167394

[Anesthesiological management of awake craniotomy : Asleep-awake-asleep technique or without sedation].

PubMed

Seemann, M; Zech, N; Graf, B; Hansen, E

2015-02-01

Awake craniotomy is indicated in deep brain stimulation (DBS) for treatment of certain movement disorders, such as in Parkinson disease patients or in the surgery of brain tumors in close vicinity to the language area. The standard procedure is the asleep-awake-asleep technique where general anesthesia or analgosedation is intermittently interrupted for neurological testing. In DBS the intraoperative improvement of symptoms, stereotactic navigation and microelectrode reading guide to the optimal position. In brain tumor resection, reversible functional impairments during electrical stimulation on the brain surface (brain mapping) show the exact individual position of eloquent or motoric areas that should be protected.The anesthesiology procedures used are very variable. It is a balancing act between overdosing of anesthetics with impairment of respiration and alertness and underdosing with pain, strain and stress for the patient. For the asleep-awake-asleep technique high acceptance but also frequent and partly severe complications have been reported. The psychological stress for the patient can be immense. Obviously, a feeling of being left alone and being at someone's mercy is not adequately treated by drugs and performance of the neurological tests is undoubtedly better and more reliable with less pharmacological impairment. Cranial nerve blocks can reduce the amount of anesthetics as they provide analgesia of the scalp more efficiently than local infiltration. With these nerve blocks, a strong therapeutic relationship and a specific communication, sedatives can be avoided and the need for opioids markedly reduced or abolished. The suggestive communication promotes for instance dissociation to an inner safe refuge, as well as reframing of disturbing noises and sensations. Each of the methods applied for awake craniotomy can profit from the principles of this awake-awake-awake technique.

Brain stimulation in posttraumatic stress disorder

PubMed Central

Novakovic, Vladan; Sher, Leo; Lapidus, Kyle A.B.; Mindes, Janet; A.Golier, Julia; Yehuda, Rachel

2011-01-01

Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in reducing anxiety, findings that may suggest possible utility in relieving PTSD-associated anxiety. Treatment of animal models of PTSD with DBS suggests potential human benefit. Additional research and novel treatment options for PTSD are urgently needed. The potential usefulness of brain stimulation in treating PTSD deserves further exploration. PMID:22893803

Deep brain stimulation and treatment-resistant obsessive-compulsive disorder: A systematic review.

PubMed

Vázquez-Bourgon, Javier; Martino, Juan; Sierra Peña, María; Infante Ceberio, Jon; Martínez Martínez, M Ángeles; Ocón, Roberto; Menchón, José Manuel; Crespo Facorro, Benedicto; Vázquez-Barquero, Alfonso

2017-07-01

At least 10% of patients with Obsessive-compulsive Disorder (OCD) are refractory to psychopharmacological treatment. The emergence of new technologies for the modulation of altered neuronal activity in Neurosurgery, deep brain stimulation (DBS), has enabled its use in severe and refractory OCD cases. The objective of this article is to review the current scientific evidence on the effectiveness and applicability of this technique to refractory OCD. We systematically reviewed the literature to identify the main characteristics of deep brain stimulation, its use and applicability as treatment for obsessive-compulsive disorder. Therefore, we reviewed PubMed/Medline, Embase and PsycINFO databases, combining the key-words 'Deep brain stimulation', 'DBS' and 'Obsessive-compulsive disorder' 'OCS'. The articles were selected by two of the authors independently, based on the abstracts, and if they described any of the main characteristics of the therapy referring to OCD: applicability; mechanism of action; brain therapeutic targets; efficacy; side-effects; co-therapies. All the information was subsequently extracted and analysed. The critical analysis of the evidence shows that the use of DBS in treatment-resistant OCD is providing satisfactory results regarding efficacy, with assumable side-effects. However, there is insufficient evidence to support the use of any single brain target over another. Patient selection has to be done following analyses of risks/benefits, being advisable to individualize the decision of continuing with concomitant psychopharmacological and psychological treatments. The use of DBS is still considered to be in the field of research, although it is increasingly used in refractory-OCD, producing in the majority of studies significant improvements in symptomatology, and in functionality and quality of life. It is essential to implement random and controlled studies regarding its long-term efficacy, cost-risk analyses and cost/benefit. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

Longitudinal atlas for normative human brain development and aging over the lifespan using quantitative susceptibility mapping.

PubMed

Zhang, Yuyao; Wei, Hongjiang; Cronin, Matthew J; He, Naying; Yan, Fuhua; Liu, Chunlei

2018-05-01

Longitudinal brain atlases play an important role in the study of human brain development and cognition. Existing atlases are mainly based on anatomical features derived from T1-and T2-weighted MRI. A 4D developmental quantitative susceptibility mapping (QSM) atlas may facilitate the estimation of age-related iron changes in deep gray matter nuclei and myelin changes in white matter. To this end, group-wise co-registered QSM templates were generated over various age intervals from age 1-83 years old. Registration was achieved by combining both T1-weighted and QSM images. Based on the proposed template, we created an accurate deep gray matter nuclei parcellation map (DGM map). Notably, we segmented thalamus into 5 sub-regions, i.e. the anterior nuclei, the median nuclei, the lateral nuclei, the pulvinar and the internal medullary lamina. Furthermore, we built a "whole brain QSM parcellation map" by combining existing cortical parcellation and white-matter atlases with the proposed DGM map. Based on the proposed QSM atlas, the segmentation accuracy of iron-rich nuclei using QSM is significantly improved, especially for children and adolescent subjects. The age-related progression of magnetic susceptibility in each of the deep gray matter nuclei, the hippocampus, and the amygdala was estimated. Our automated atlas-based analysis provided a systematic confirmation of previous findings on susceptibility progression with age resulting from manual ROI drawings in deep gray matter nuclei. The susceptibility development in the hippocampus and the amygdala follow an iron accumulation model; while in the thalamus sub-regions, the susceptibility development exhibits a variety of trends. It is envisioned that the newly developed 4D QSM atlas will serve as a template for studying brain iron deposition and myelination/demyelination in both normal aging and various brain diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Monitoring brain temperature by time-resolved near-infrared spectroscopy: pilot study

NASA Astrophysics Data System (ADS)

Bakhsheshi, Mohammad Fazel; Diop, Mamadou; St. Lawrence, Keith; Lee, Ting-Yim

2014-05-01

Mild hypothermia (HT) is an effective neuroprotective strategy for a variety of acute brain injuries. However, the wide clinical adaptation of HT has been hampered by the lack of a reliable noninvasive method for measuring brain temperature, since core measurements have been shown to not always reflect brain temperature. The goal of this work was to develop a noninvasive optical technique for measuring brain temperature that exploits both the temperature dependency of water absorption and the high concentration of water in brain (80%-90%). Specifically, we demonstrate the potential of time-resolved near-infrared spectroscopy (TR-NIRS) to measure temperature in tissue-mimicking phantoms (in vitro) and deep brain tissue (in vivo) during heating and cooling, respectively. For deep brain tissue temperature monitoring, experiments were conducted on newborn piglets wherein hypothermia was induced by gradual whole body cooling. Brain temperature was concomitantly measured by TR-NIRS and a thermocouple probe implanted in the brain. Our proposed TR-NIRS method was able to measure the temperature of tissue-mimicking phantoms and brain tissues with a correlation of 0.82 and 0.66 to temperature measured with a thermometer, respectively. The mean difference between the TR-NIRS and thermometer measurements was 0.15°C±1.1°C for the in vitro experiments and 0.5°C±1.6°C for the in vivo measurements.

Brain activity monitoring by compressed spectral array during deep hypothermic circulatory arrest in acute aortic dissection surgery.

PubMed

Urbanowicz, Tomasz K; Budniak, Wiktor; Buczkowski, Piotr; Perek, Bartłomiej; Walczak, Maciej; Tomczyk, Jadwiga; Katarzyński, Sławomir; Jemielity, Marek

2014-12-01

Monitoring the central nervous system during aortic dissection repair may improve the understanding of the intraoperative changes related to its bioactivity. The aim of the study was to evaluate the influence of deep hypothermia on intraoperative brain bioactivity measured by the compressed spectral array (CSA) method and to assess the influence of the operations on postoperative cognitive function. The study enrolled 40 patients (31 men and 9 women) at the mean age of 60.2 ± 8.6 years, diagnosed with acute aortic dissection. They underwent emergency operations in deep hypothermic circulatory arrest (DHCA). During the operations, brain bioactivity was monitored with the compressed spectral array method. There were no intraoperative deaths. Electrocerebral silence during DHCA was observed in 31 patients (74%). The lowest activity was observed during DHCA: it was 0.01 ± 0.05 nW in the left hemisphere and 0.01 ± 0.03 nW in the right hemisphere. The postoperative results of neurological tests deteriorated statistically significantly (26.9 ± 1.7 points vs. 22.0 ± 1.7 points; p < 0.001), especially among patients who exhibited brain activity during DHCA. The compressed spectral array method is clinically useful in monitoring brain bioactivity during emergency operations of acute aortic dissections. Electrocerebral silence occurs in 75% of patients during DHCA. The cognitive function of patients deteriorates significantly after operations with DHCA.

Deep brain stimulation reveals emotional impact processing in ventromedial prefrontal cortex.

PubMed

Gjedde, Albert; Geday, Jacob

2009-12-07

We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin-noradrenaline reuptake sites. We tested the hypothesis in patients with Parkinson's disease in whom we had measured the changes of blood flow everywhere in the brain associated with the deep brain stimulation of the subthalamic nucleus. We determined the emotional reactivity of the patients as the average impact of emotive images rated by the patients off the DBS. We then searched for sites in the brain that had significant correlation of the changes of blood flow with the emotional impact rated by the patients. The results indicate a significant link between the emotional impact when patients are not stimulated and the change of blood flow associated with the DBS. In subjects with a low emotional impact, activity measured as blood flow rose when the electrode was turned on, while in subjects of high impact, the activity at this site in the ventromedial prefrontal cortex declined when the electrode was turned on. We conclude that changes of neurotransmission in the ventromedial prefrontal cortex had an effect on the tissue that depends on changes of monoamine concentration interacting with specific combinations of inhibitory and excitatory monoamine receptors.

Deep brain stimulation for psychiatric disorders: where we are now.

PubMed

Cleary, Daniel R; Ozpinar, Alp; Raslan, Ahmed M; Ko, Andrew L

2015-06-01

Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

A Comparison of Peak Electric Fields and GICs in the Pacific Northwest Using 1-D and 3-D Conductivity

NASA Astrophysics Data System (ADS)

Gannon, J. L.; Birchfield, A. B.; Shetye, K. S.; Overbye, T. J.

2017-11-01

Geomagnetically induced currents (GICs) are a result of the changing magnetic fields during a geomagnetic disturbance interacting with the deep conductivity structures of the Earth. When assessing GIC hazard, it is a common practice to use layer-cake or one-dimensional conductivity models to approximate deep Earth conductivity. In this paper, we calculate the electric field and estimate GICs induced in the long lines of a realistic system model of the Pacific Northwest, using the traditional 1-D models, as well as 3-D models represented by Earthscope's Electromagnetic transfer functions. The results show that the peak electric field during a given event has considerable variation across the analysis region in the Pacific Northwest, but the 1-D physiographic approximations may accurately represent the average response of an area, although corrections are needed. Rotations caused by real deep Earth conductivity structures greatly affect the direction of the induced electric field. This effect may be just as, or more, important than peak intensity when estimating GICs induced in long bulk power system lines.

75 FR 4407 - The Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-27

... premarket approval application for the Deep Brain Stimulation System for Epilepsy sponsored by Medtronic...-onset seizures (affecting only a part of the brain when they begin), with or without secondary... a partial-onset seizure that later spreads to the whole brain. ``Refractory'' to antiepileptic...

Electrical bioimpedance enabling prompt intervention in traumatic brain injury

NASA Astrophysics Data System (ADS)

Seoane, Fernando; Atefi, S. Reza

2017-05-01

Electrical Bioimpedance (EBI) is a well spread technology used in clinical practice across the world. Advancements in Textile material technology with conductive textile fabrics and textile-electronics integration have allowed exploring potential applications for Wearable Measurement Sensors and Systems exploiting. The sensing principle of electrical bioimpedance is based on the intrinsic passive dielectric properties of biological tissue. Using a pair of electrodes, tissue is electrically stimulated and the electrical response can be sensed with another pair of surface electrodes. EBI spectroscopy application for cerebral monitoring of neurological conditions such as stroke and perinatal asphyxia in newborns have been justified using animal studies and computational simulations. Such studies have shown proof of principle that neurological pathologies indeed modify the dielectric composition of the brain that is detectable via EBI. Similar to stroke, Traumatic Brain Injury (TBI) also affects the dielectric properties of brain tissue that can be detected via EBI measurements. Considering the portable and noninvasive characteristics of EBI it is potentially useful for prehospital triage of TBI patients where. In the battlefield blast induced Traumatic Brain Injuries are very common. Brain damage must be assessed promptly to have a chance to prevent severe damage or eventually death. The relatively low-complexity of the sensing hardware required for EBI sensing and the already proven compatibility with textile electrodes suggest the EBI technology is indeed a candidate for developing a handheld device equipped with a sensorized textile cap to produce an examination in minutes for enabling medically-guided prompt intervention.

A deep convolutional neural network-based automatic delineation strategy for multiple brain metastases stereotactic radiosurgery

PubMed Central

Stojadinovic, Strahinja; Hrycushko, Brian; Wardak, Zabi; Lau, Steven; Lu, Weiguo; Yan, Yulong; Jiang, Steve B.; Zhen, Xin; Timmerman, Robert; Nedzi, Lucien

2017-01-01

Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS) treatment planning. In this work, we developed a deep learning convolutional neural network (CNN) algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI) datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS) data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs) of 0.75±0.07 in the tumor core and 0.81±0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67±0.03 and achieved an area under the receiver operating characteristic curve of 0.98±0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases. PMID:28985229

Brain tumor segmentation in multi-spectral MRI using convolutional neural networks (CNN).

PubMed

Iqbal, Sajid; Ghani, M Usman; Saba, Tanzila; Rehman, Amjad

2018-04-01

A tumor could be found in any area of the brain and could be of any size, shape, and contrast. There may exist multiple tumors of different types in a human brain at the same time. Accurate tumor area segmentation is considered primary step for treatment of brain tumors. Deep Learning is a set of promising techniques that could provide better results as compared to nondeep learning techniques for segmenting timorous part inside a brain. This article presents a deep convolutional neural network (CNN) to segment brain tumors in MRIs. The proposed network uses BRATS segmentation challenge dataset which is composed of images obtained through four different modalities. Accordingly, we present an extended version of existing network to solve segmentation problem. The network architecture consists of multiple neural network layers connected in sequential order with the feeding of Convolutional feature maps at the peer level. Experimental results on BRATS 2015 benchmark data thus show the usability of the proposed approach and its superiority over the other approaches in this area of research. © 2018 Wiley Periodicals, Inc.

Visualization of cortical, subcortical, and deep brain neural circuit dynamics during naturalistic mammalian behavior with head-mounted microscopes and chronically implanted lenses

PubMed Central

Resendez, Shanna L.; Jennings, Josh H.; Ung, Randall L.; Namboodiri, Vijay Mohan K.; Zhou, Zhe Charles; Otis, James M.; Nomura, Hiroshi; McHenry, Jenna A.; Kosyk, Oksana; Stuber, Garret D.

2016-01-01

Genetically encoded calcium indicators for visualizing dynamic cellular activity have greatly expanded our understanding of the brain. However, due to light scattering properties of the brain as well as the size and rigidity of traditional imaging technology, in vivo calcium imaging has been limited to superficial brain structures during head fixed behavioral tasks. This limitation can now be circumvented by utilizing miniature, integrated microscopes in conjunction with an implantable microendoscopic lens to guide light into and out of the brain, thus permitting optical access to deep brain (or superficial) neural ensembles during naturalistic behaviors. Here, we describe procedural steps to conduct such imaging studies using mice. However, we anticipate the protocol can be easily adapted for use in other small vertebrates. Successful completion of this protocol will permit cellular imaging of neuronal activity and the generation of data sets with sufficient statistical power to correlate neural activity with stimulus presentation, physiological state, and other aspects of complex behavioral tasks. This protocol takes 6–11 weeks to complete. PMID:26914316

Brain electric microstates and momentary conscious mind states as building blocks of spontaneous thinking: I. Visual imagery and abstract thoughts.

PubMed

Lehmann, D; Strik, W K; Henggeler, B; Koenig, T; Koukkou, M

1998-06-01

Prompted reports of recall of spontaneous, conscious experiences were collected in a no-input, no-task, no-response paradigm (30 random prompts to each of 13 healthy volunteers). The mentation reports were classified into visual imagery and abstract thought. Spontaneous 19-channel brain electric activity (EEG) was continuously recorded, viewed as series of momentary spatial distributions (maps) of the brain electric field and segmented into microstates, i.e. into time segments characterized by quasi-stable landscapes of potential distribution maps which showed varying durations in the sub-second range. Microstate segmentation used a data-driven strategy. Different microstates, i.e. different brain electric landscapes must have been generated by activity of different neural assemblies and therefore are hypothesized to constitute different functions. The two types of reported experiences were associated with significantly different microstates (mean duration 121 ms) immediately preceding the prompts; these microstates showed, across subjects, for abstract thought (compared to visual imagery) a shift of the electric gravity center to the left and a clockwise rotation of the field axis. Contrariwise, the microstates 2 s before the prompt did not differ between the two types of experiences. The results support the hypothesis that different microstates of the brain as recognized in its electric field implement different conscious, reportable mind states, i.e. different classes (types) of thoughts (mentations); thus, the microstates might be candidates for the 'atoms of thought'.

Deep rock nuclear waste disposal test: design and operation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klett, Robert D.

1974-09-01

An electrically heated test of nuclear waste simulants in granitic rock was conducted to demonstrate the feasibility of the concept of deep rock nuclear waste disposal and to obtain design data. This report describes the deep rock disposal sytstems study and the design and operation of the first concept feasibility test.

Symptoms and Treatment | NIH MedlinePlus the Magazine

MedlinePlus

... of this page please turn JavaScript on. Feature: Parkinson's Disease Symptoms and Treatment Past Issues / Winter 2016 Table ... study to identify abnormal brain rhythms associated with Parkinson's disease. Photo courtesy of Coralie de Hemptinne Deep Brain ...

A testbed to explore the optimal electrical stimulation parameters for suppressing inter-ictal spikes in human hippocampal slices.

PubMed

Min-Chi Hsiao; Pen-Ning Yu; Dong Song; Liu, Charles Y; Heck, Christi N; Millett, David; Berger, Theodore W

2014-01-01

New interventions using neuromodulatory devices such as vagus nerve stimulation, deep brain stimulation and responsive neurostimulation are available or under study for the treatment of refractory epilepsy. Since the actual mechanisms of the onset and termination of the seizure are still unclear, most researchers or clinicians determine the optimal stimulation parameters through trial-and-error procedures. It is necessary to further explore what types of electrical stimulation parameters (these may include stimulation frequency, amplitude, duration, interval pattern, and location) constitute a set of optimal stimulation paradigms to suppress seizures. In a previous study, we developed an in vitro epilepsy model using hippocampal slices from patients suffering from mesial temporal lobe epilepsy. Using a planar multi-electrode array system, inter-ictal activity from human hippocampal slices was consistently recorded. In this study, we have further transferred this in vitro seizure model to a testbed for exploring the possible neurostimulation paradigms to inhibit inter-ictal spikes. The methodology used to collect the electrophysiological data, the approach to apply different electrical stimulation parameters to the slices are provided in this paper. The results show that this experimental testbed will provide a platform for testing the optimal stimulation parameters of seizure cessation. We expect this testbed will expedite the process for identifying the most effective parameters, and may ultimately be used to guide programming of new stimulating paradigms for neuromodulatory devices.

Recurrent, Delayed Hemorrhage Associated with Edoxaban after Deep Brain Stimulation Lead Placement

PubMed Central

Garber, Sarah T.; Schrock, Lauren E.; House, Paul A.

2013-01-01

Factor-Xa inhibitors like edoxaban have been shown to have comparable or superior rates of stroke and systemic embolization prevention to warfarin while exhibiting lower clinically significant bleeding rates. The authors report a case of a man who presented with delayed, recurrent intracranial hemorrhage months after successful deep brain stimulator placement for Parkinson disease while on edoxaban for atrial fibrillation. Further reports on the use of novel anticoagulants after intracranial surgery are acutely needed to help assess the true relative risk they pose. PMID:23365773

Current Topics in Deep Brain Stimulation for Parkinson Disease

PubMed Central

UMEMURA, Atsushi; OYAMA, Genko; SHIMO, Yasushi; NAKAJIMA, Madoka; NAKAJIMA, Asuka; JO, Takayuki; SEKIMOTO, Satoko; ITO, Masanobu; MITSUHASHI, Takumi; HATTORI, Nobutaka; ARAI, Hajime

2016-01-01

There is a long history of surgical treatment for Parkinson disease (PD). After pioneering trials and errors, the current primary surgical treatment for PD is deep brain stimulation (DBS). DBS is a promising treatment option for patients with medically refractory PD. However, there are still many problems and controversies associated with DBS. In this review, we discuss current issues in DBS for PD, including patient selection, clinical outcomes, complications, target selection, long-term outcomes, management of axial symptoms, timing of surgery, surgical procedures, cost-effectiveness, and new technology. PMID:27349658

Stridor and dysphagia associated with subthalamic nucleus stimulation in Parkinson disease.

PubMed

Fagbami, Oluwakemi Y; Donato, Anthony A

2011-11-01

Refractory symptoms in Parkinson disease show good response to deep brain stimulation (DBS). This procedure improves United Parkinson's Disease Rating Scale scores and reduces dyskinesias, whereas speech and swallowing dysfunction typically do not improve and may even worsen. Rarely, DBS can cause idiosyncratic dystonias of muscle groups, including those of the neck and throat. The authors describe a patient experiencing stridor and dysphagia with confirmed pulmonary restriction and aspiration following subthalamic nucleus deep brain stimulator adjustment, with a resolution of symptoms and signs when the stimulator was switched off.

Deep Brain Stimulation using Magnetic Fields

NASA Astrophysics Data System (ADS)

Jiles, David; Williams, Paul; Crowther, Lawrence; Iowa State University Team; Wolfson CentreMagnetics Team

2011-03-01

New applications for transcranial magnetic stimulation are developing rapidly for both diagnostic and therapeutic purposes. Therefore so is the demand for improved performance, particularly in terms of their ability to stimulate deeper regions of the brain and to do so selectively. The coil designs that are used presently are limited in their ability to stimulate the brain at depth and with high spatial focality. Consequently, any improvement in coil performance would have a significant impact in extending the usefulness of TMS in both clinical applications and academic research studies. New and improved coil designs have then been developed, modeled and tested as a result of this work. A large magnetizing coil, 300mm in diameter and compatible with a commercial TMS system has been constructed to determine its feasibility for use as a deep brain stimulator. The results of this work have suggested directions that could be pursued in order to further improve the coil designs.

Deep sequencing reveals persistence of cell-associated mumps vaccine virus in chronic encephalitis.

PubMed

Morfopoulou, Sofia; Mee, Edward T; Connaughton, Sarah M; Brown, Julianne R; Gilmour, Kimberly; Chong, W K 'Kling'; Duprex, W Paul; Ferguson, Deborah; Hubank, Mike; Hutchinson, Ciaran; Kaliakatsos, Marios; McQuaid, Stephen; Paine, Simon; Plagnol, Vincent; Ruis, Christopher; Virasami, Alex; Zhan, Hong; Jacques, Thomas S; Schepelmann, Silke; Qasim, Waseem; Breuer, Judith

2017-01-01

Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV JL5 ) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuV JL5 associated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines. The diagnosis was only possible by deep sequencing of the brain biopsy. Sequence comparison of the vaccine batch to the MuV JL5 isolated from brain identified biased hypermutation, particularly in the matrix gene, similar to those found in measles from cases of SSPE. The findings provide unique insights into the pathogenesis of paramyxovirus brain infections.

Temporally Coordinated Deep Brain Stimulation in the Dorsal and Ventral Striatum Synergistically Enhances Associative Learning.

PubMed

Katnani, Husam A; Patel, Shaun R; Kwon, Churl-Su; Abdel-Aziz, Samer; Gale, John T; Eskandar, Emad N

2016-01-04

The primate brain has the remarkable ability of mapping sensory stimuli into motor behaviors that can lead to positive outcomes. We have previously shown that during the reinforcement of visual-motor behavior, activity in the caudate nucleus is correlated with the rate of learning. Moreover, phasic microstimulation in the caudate during the reinforcement period was shown to enhance associative learning, demonstrating the importance of temporal specificity to manipulate learning related changes. Here we present evidence that extends upon our previous finding by demonstrating that temporally coordinated phasic deep brain stimulation across both the nucleus accumbens and caudate can further enhance associative learning. Monkeys performed a visual-motor associative learning task and received stimulation at time points critical to learning related changes. Resulting performance revealed an enhancement in the rate, ceiling, and reaction times of learning. Stimulation of each brain region alone or at different time points did not generate the same effect.

Deep Brain Stimulation

PubMed Central

Lyketsos, Constantine G.; Pendergrass, Jo Cara; Lozano, Andres M.

2012-01-01

Recent studies have identified an association between memory deficits and defects of the integrated neuronal cortical areas known collectively as the default mode network. It is conceivable that the amyloid deposition or other molecular abnormalities seen in patients with Alzheimer’s disease may interfere with this network and disrupt neuronal circuits beyond the localized brain areas. Therefore, Alzheimer’s disease may be both a degenerative disease and a broader system-level disorder affecting integrated neuronal pathways involved in memory. In this paper, we describe the rationale and provide some evidence to support the study of deep brain stimulation of the hippocampal fornix as a novel treatment to improve neuronal circuitry within these integrated networks and thereby sustain memory function in early Alzheimer’s disease. PMID:23346514

Sapphire implant based neuro-complex for deep-lying brain tumors phototheranostics

NASA Astrophysics Data System (ADS)

Sharova, A. S.; Maklygina, YU S.; Yusubalieva, G. M.; Shikunova, I. A.; Kurlov, V. N.; Loschenov, V. B.

2018-01-01

The neuro-complex as a combination of sapphire implant optical port and osteoplastic biomaterial "Collapan" as an Aluminum phthalocyanine nanoform photosensitizer (PS) depot was developed within the framework of this study. The main goals of such neuro-complex are to provide direct access of laser radiation to the brain tissue depth and to transfer PS directly to the pathological tissue location that will allow multiple optical phototheranostics of the deep-lying tumor region without repeated surgical intervention. The developed complex spectral-optical properties research was carried out by photodiagnostics method using the model sample: a brain tissue phantom. The optical transparency of sapphire implant allows obtaining a fluorescent signal with high accuracy, comparable to direct measurement "in contact" with the tissue.

Deep brain stimulation of nucleus accumbens region in alcoholism affects reward processing.

PubMed

Heldmann, Marcus; Berding, Georg; Voges, Jürgen; Bogerts, Bernhard; Galazky, Imke; Müller, Ulf; Baillot, Gunther; Heinze, Hans-Jochen; Münte, Thomas F

2012-01-01

The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H(2)[(15)O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control.

Static Electric Fields and Lightning Over Land and Ocean in Florida Thunderstorms

NASA Technical Reports Server (NTRS)

Wilson, J. G.; Cummins, K. L.; Simpson, A. A.; Hinckley, A.

2017-01-01

Natural cloud-to-ground (CG) lightning and the charge structure of the associated clouds behave differently over land and ocean. Existing literature has raised questions over the years on the behavior of thunderstorms and lightning over oceans, and there are still open scientific questions. We expand on the observational datasets by obtaining identical electric field observations over coastal land, near-shore, and deep ocean regions during both clear air and thunderstorm periods. Oceanic observations were obtained using two 3-meter NOAA buoys that were instrumented with Campbell Scientific electric field mills to measure the static electric fields. These data were compared to selected electric field records from the existing on-shore electric field mill suite of 31 sensors at Kennedy Space Center (KSC). CG lightning occurrence times, locations and peak current values for both on-shore and ocean were provided by the U.S. National Lightning Detection Network. The buoy instruments were first evaluated on-shore at the Florida coast, to calibrate field enhancements and to confirm proper behavior of the system in elevated-field environments. The buoys were then moored 20NM and 120NM off the coast of KSC in February (20NM) and August (120NM) 2014. Statistically larger CG peak currents were reported over the deep ocean for first strokes and for subsequent strokes with new contacts points. Storm-related static fields were significantly larger at both oceanic sites, likely due to decreased screening by nearby space charge. Time-evolution of the static field during storm development and propagation indicated weak or missing lower positive charge regions in most storms that initiated over the deep ocean, supporting one mechanism for the observed high peak currents in negative first strokes over the deep ocean. This project also demonstrated the practicality of off-shore electric field measurements for safety-related decision making at KSC.

Deep intracerebral (basal ganglia) haematomas in fatal non-missile head injury in man.

PubMed Central

Adams, J H; Doyle, D; Graham, D I; Lawrence, A E; McLellan, D R

1986-01-01

Deep intracerebral (basal ganglia) haematomas were found post mortem in 63 of 635 fatal non-missile head injuries. In patients with a basal ganglia haematoma, contusions were more severe, there was a reduced incidence of a lucid interval, and there was an increased incidence of road traffic accidents, gliding contusions and diffuse axonal injury than in patients without this type of haematoma. Intracranial haematoma is usually thought to be a secondary event, that is a complication of the original injury, but these results suggest that a deep intracerebral haematoma is a primary event. If a deep intracerebral haematoma is identified on an early CT scan it is likely that the patient has sustained severe diffuse brain damage at the time of injury. In the majority of head injuries damage to blood vessels or axons predominates. In patients with a traumatic deep intracerebral haematoma, it would appear that the deceleration/acceleration forces are such that both axons and blood vessels within the brain are damaged at the time of injury. Images PMID:3760892

Concentrators Enhance Solar Power Systems

NASA Technical Reports Server (NTRS)

2013-01-01

"Right now, solar electric propulsion is being looked at very seriously," says Michael Piszczor, chief of the photovoltaic and power technologies branch at Glen Research Center. The reason, he explains, originates with a unique NASA mission from the late 1990s. In 1998, the Deep Space 1 spacecraft launched from Kennedy Space Center to test a dozen different space technologies, including SCARLET, or the Solar Concentrator Array with Refractive Linear Element Technology. As a solar array that focused sunlight on a smaller solar cell to generate electric power, SCARLET not only powered Deep Space 1 s instruments but also powered its ion engine, which propelled the spacecraft throughout its journey. Deep Space 1 was the first spacecraft powered by a refractive concentrator design like SCARLET, and also utilized multi-junction solar cells, or cells made of multiple layers of different materials. For the duration of its 38-month mission, SCARLET performed flawlessly, even as Deep Space 1 flew by Comet Borrelly and Asteroid Braille. "Everyone remembers the ion engine on Deep Space 1, but they tend to forget that the SCARLET array powered it," says Piszczor. "Not only did both technologies work as designed, but the synergy between the two, solar power and propulsion together, is really the important aspect of this technology demonstration mission. It was the first successful use of solar electric propulsion for primary propulsion." More than a decade later, NASA is keenly interested in using solar electric propulsion (SEP) for future space missions. A key issue is cost, and SEP has the potential to substantially reduce cost compared to conventional chemical propulsion technology. "SEP allows you to use spacecraft that are smaller, lighter, and less costly," says Piszczor. "Even though it might take longer to get somewhere using SEP, if you are willing to trade time for cost and smaller vehicles, it s a good trade." Potentially, SEP could be used on future science missions in orbit around the Earth or Moon, to planets or asteroids, on deep space science missions, and even on exploration missions. In fact, electric propulsion is already being used on Earth-orbiting satellites for positioning.

Perioperative Brain Shift and Deep Brain Stimulating Electrode Deformation Analysis: Implications for rigid and non-rigid devices

PubMed Central

Sillay, Karl A.; Kumbier, L. M.; Ross, C.; Brady, M.; Alexander, A.; Gupta, A.; Adluru, N.; Miranpuri, G. S.; Williams, J. C.

2016-01-01

Deep brain stimulation (DBS) efficacy is related to optimal electrode placement. Several authors have quantified brain shift related to surgical targeting; yet, few reports document and discuss the effects of brain shift after insertion. Objective: To quantify brain shift and electrode displacement after device insertion. Twelve patients were retrospectively reviewed, and one post-operative MRI and one time-delayed CT were obtained for each patient and their implanted electrodes modeled in 3D. Two competing methods were employed to measure the electrode tip location and deviation from the prototypical linear implant after the resolution of acute surgical changes, such as brain shift and pneumocephalus. In the interim between surgery and a pneumocephalus free postoperative scan, electrode deviation was documented in all patients and all electrodes. Significant shift of the electrode tip was identified in rostral, anterior, and medial directions (p < 0.05). Shift was greatest in the rostral direction, measuring an average of 1.41 mm. Brain shift and subsequent electrode displacement occurs in patients after DBS surgery with the reversal of intraoperative brain shift. Rostral displacement is on the order of the height of one DBS contact. Further investigation into the time course of intraoperative brain shift and its potential effects on procedures performed with rigid and non-rigid devices in supine and semi-sitting surgical positions is needed. PMID:23010803

Deep brain stimulation of the inferior colliculus: a possible animal model to study paradoxical kinesia observed in some parkinsonian patients?

PubMed

Melo-Thomas, Liana; Thomas, Uwe

2015-02-15

The inferior colliculus (IC) plays an important role in the normal processing of the acoustic message and is also involved in the filtering of acoustic stimuli of aversive nature. The neural substrate of the IC can also influence haloperidol-induced catalepsy. Considering that (i) paradoxical kinesia, observed in some parkinsonian patients, seems to be dependent of their emotional state and (ii) deep brain stimulation (DBS) represents an alternative therapeutic route for the relief of parkinsonian symptoms, the present study investigated the consequence of DBS at the IC on the catalepsy induced by haloperidol in rats. Additionally, we investigated if DBS of the IC can elicit motor responses in anesthetized rats and whether DBS elicits distinct neural firing patterns of activity at the dorsal cortex (DCIC) or central nucleus (CNIC) of the IC. A significant reduction of the catalepsy response was seen in rats previously given haloperidol and receiving DBS at the IC. In addition, electrical stimulation to the ventral part of the CNIC induced immediate motor responses in anesthetized rats. The neuronal spontaneous activity was higher at the ventral part of the CNIC than the dorsal part. DBS to the ventral part but not to the dorsal part of the CNIC increased the spike rate at neurons a few hundred microns away from the stimulation site. It is possible that the IC plays a role in the sensorimotor gating activated by emotional stimuli, and that DBS at the IC can be a promising new animal model to study paradoxical kinesia in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

Modeling deep brain stimulation: point source approximation versus realistic representation of the electrode

NASA Astrophysics Data System (ADS)

Zhang, Tianhe C.; Grill, Warren M.

2010-12-01

Deep brain stimulation (DBS) has emerged as an effective treatment for movement disorders; however, the fundamental mechanisms by which DBS works are not well understood. Computational models of DBS can provide insights into these fundamental mechanisms and typically require two steps: calculation of the electrical potentials generated by DBS and, subsequently, determination of the effects of the extracellular potentials on neurons. The objective of this study was to assess the validity of using a point source electrode to approximate the DBS electrode when calculating the thresholds and spatial distribution of activation of a surrounding population of model neurons in response to monopolar DBS. Extracellular potentials in a homogenous isotropic volume conductor were calculated using either a point current source or a geometrically accurate finite element model of the Medtronic DBS 3389 lead. These extracellular potentials were coupled to populations of model axons, and thresholds and spatial distributions were determined for different electrode geometries and axon orientations. Median threshold differences between DBS and point source electrodes for individual axons varied between -20.5% and 9.5% across all orientations, monopolar polarities and electrode geometries utilizing the DBS 3389 electrode. Differences in the percentage of axons activated at a given amplitude by the point source electrode and the DBS electrode were between -9.0% and 12.6% across all monopolar configurations tested. The differences in activation between the DBS and point source electrodes occurred primarily in regions close to conductor-insulator interfaces and around the insulating tip of the DBS electrode. The robustness of the point source approximation in modeling several special cases—tissue anisotropy, a long active electrode and bipolar stimulation—was also examined. Under the conditions considered, the point source was shown to be a valid approximation for predicting excitation of populations of neurons in response to DBS.

Zolpidem improves neuropsychiatric symptoms and motor dysfunction in a patient with Parkinson's disease after deep brain stimulation.

PubMed

Huang, Hung-Yu; Hsu, Yi-Ting; Wu, Yu-Chin; Chiou, Shang-Ming; Kao, Chia-Hung; Tsai, Mu-Chieh; Tsai, Chon-Haw

2012-06-01

To illustrate the beneficial effect of zolpidem on the neuropsychiatric and motor symptoms in a patient with Parkinson disease (PD) after bilateral subthalamic nucleus deep brain stimulation. The 61-year-old housewife was diagnosed to have PD for 12 years with initial presentation of clumsiness and rest tremor of right limbs. She was referred to our hospital in March 2009 due to shortening of drug beneficial period since 3 years ago and on-phase dyskinesia in recent 2 years. Bilateral STN DBS was conducted on 18 June, 2009. Fluctuating spells of mental confusion were developed on the next day after surgery. Electric stimuli via DBS electrodes were delivered with parameters of 2 volts, 60 μs, 130 Hz on bilateral STN 32 days after DBS. The incoherent behaviors and motor fluctuation remained to occur. The beneficial effect of zolpidem on her neuropsychiatric and motor symptoms was detected incidentally in early July 2009. She could chat normally with her caregiver and walk with assistance after taking zolpidem. The beneficial period may last for 2 hours. Zolpidem was then given in dosage of 10 mg three times per day. The neuropsychiatric inventory was scored 56 during zolpidem 'off' and 30 during zolpidem 'on'. To understand the intriguing feature, we conducted FDG-PET during 'off' and 'on' zolpidem conditions. The results revealed that the metabolism was decreased in the right frontal, parietal cortex and caudate nucleus during zolpidem 'off'. These cool spots can be partially restored by zolpidem. Zolpidem ameliorated the neuropsychiatric and parkinsonian motor symptom in the PD patient. Since GABAA benzodiazepine receptors are widely distributed throughout the central nervous system, zolpidem probably acts via modulating structures lying within the cortico-subcortical loop or by direct effect on these cortical regions.

Cavitation of deep lacunar infarcts in patients with first-ever lacunar stroke: a 2-year follow-up study with MR.

PubMed

Loos, Caroline M J; Staals, Julie; Wardlaw, Joanna M; van Oostenbrugge, Robert J

2012-08-01

Studies in patients with lacunar stroke often assess the number of lacunes. However, data on how many symptomatic lacunar infarcts cavitate into a lacune are limited. We assessed the evolution of symptomatic lacunar infarcts over 2-year follow-up. In 82 patients with first-ever lacunar stroke with a lacunar infarct in the deep brain regions (excluding the centrum semiovale), we performed a brain MR at presentation and 2 years later. We classified cavitation of lacunar infarcts at baseline and on follow-up MR as absent, incomplete, or complete. We recorded time to imaging, infarct size, and vascular risk factors. On baseline MR, 38 (46%) index infarcts showed complete or incomplete cavitation. Median time to imaging was 8 (0-73) days in noncavitated and 63 (1-184) days in cavitated lesions (P<0.05). On follow-up imaging, 94% of the lacunar infarcts were completely or incompletely cavitated, most had reduced in diameter, and 5 (6%) had disappeared. Vascular risk factors were not associated with cavitation. Cavitation and lesion shrinkage were seen in almost all symptomatic lacunar infarcts in the deep brain regions over 2-year follow-up. Counting lacunes in these specific regions at a random moment might slightly, however not substantially, underestimate the burden of deep lacunar infarction.

Effect of diet with omega-3 in basal brain electrical activity and during status epilepticus in rats.

PubMed

Pessoa, Daniella Tavares; da Silva, Eva Luana Almeida; Costa, Edbhergue Ventura Lola; Nogueira, Romildo Albuquerque

2017-11-01

Western diets are high in saturated fat and low in omega-3. Certain animals cannot produce omega-3 from their own lipids, making it necessary for it to be acquired from the diet. However, omega-3s are important components of the plasma membrane, and altering their proportions can promote physical and chemical alterations in the membranes, which may modify neuronal excitability. These alterations occur in healthy individuals, as well as in patients with epilepsy who are more sensitive to changes in brain electrical activity. This study evaluated the effect of a diet supplemented with omega-3 on the basal brain electrical activity both before and during status epilepticus in rats. To evaluate the brain electrical activity, we recorded electrocorticograms (ECoG) of animals both with and without omega-3 supplementation before and during status epilepticus induced by pilocarpine. Calculation of the average brain wave power by a power spectrum revealed that omega-3 supplementation reduced the average power of the delta wave by 20% and increased the average power of the beta wave by 45%. These effects were exacerbated when status epilepticus was induced in the animals supplemented with omega-3. The animals with and without omega-3 supplementation exhibited increases in basal brain electrical activities during status epilepticus. The two groups showed hyperactivity, but no significant difference between them was noted. Even though the brain activity levels observed during status epilepticus were similar between the two groups, neuron damage to the animals supplemented with omega-3 was more slight, revealing the neuroprotective effect of the omega-3. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of electrolysis time and electric potential on chlorine generation of electrolyzed deep ocean water.

PubMed

Hsu, Guoo-Shyng Wang; Lu, Yi-Fa; Hsu, Shun-Yao

2017-10-01

Electrolyzed water is a sustainable disinfectant, which can comply with food safety regulations and is environmentally friendly. A two-factor central composite design was adopted for studying the effects of electrolysis time and electric potential on the chlorine generation efficiency of electrolyzed deep ocean water (DOW). DOW was electrolyzed in a glass electrolyzing cell equipped with platinum-plated titanium anode and cathode. The results showed that chlorine concentration reached maximal level in the batch process. Prolonged electrolysis reduced chlorine concentration in the electrolyte and was detrimental to electrolysis efficiency, especially under high electric potential conditions. Therefore, the optimal choice of electrolysis time depends on the electrolyzable chloride in DOW and cell potential adopted for electrolysis. The higher the electric potential, the faster the chlorine level reaches its maximum, but the lower the electric efficiency will be. Copyright © 2016. Published by Elsevier B.V.

Capacitance spectroscopy on n-type GaNAs/GaAs embedded quantum structure solar cells

NASA Astrophysics Data System (ADS)

Venter, Danielle; Bollmann, Joachim; Elborg, Martin; Botha, J. R.; Venter, André

2018-04-01

In this study, both deep level transient spectroscopy (DLTS) and admittance spectroscopy (AS) have been used to study the properties of electrically active deep level centers present in GaNAs/GaAs quantum wells (QWs) embedded in p-i-n solar cells. The structures were grown by molecular beam epitaxy (MBE). In particular, the electrical properties of samples with Si (n-type) doping of the QWs were investigated. DLTS revealed four deep level centers in the material, whereas only three were detected by AS. NextNano++ simulation software was used to model the sample band-diagrams to provide reasoning for the origin of the signals produced by both techniques.

Deep Convolutional Neural Networks for Multi-Modality Isointense Infant Brain Image Segmentation

PubMed Central

Zhang, Wenlu; Li, Rongjian; Deng, Houtao; Wang, Li; Lin, Weili; Ji, Shuiwang; Shen, Dinggang

2015-01-01

The segmentation of infant brain tissue images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) plays an important role in studying early brain development in health and disease. In the isointense stage (approximately 6–8 months of age), WM and GM exhibit similar levels of intensity in both T1 and T2 MR images, making the tissue segmentation very challenging. Only a small number of existing methods have been designed for tissue segmentation in this isointense stage; however, they only used a single T1 or T2 images, or the combination of T1 and T2 images. In this paper, we propose to use deep convolutional neural networks (CNNs) for segmenting isointense stage brain tissues using multi-modality MR images. CNNs are a type of deep models in which trainable filters and local neighborhood pooling operations are applied alternatingly on the raw input images, resulting in a hierarchy of increasingly complex features. Specifically, we used multimodality information from T1, T2, and fractional anisotropy (FA) images as inputs and then generated the segmentation maps as outputs. The multiple intermediate layers applied convolution, pooling, normalization, and other operations to capture the highly nonlinear mappings between inputs and outputs. We compared the performance of our approach with that of the commonly used segmentation methods on a set of manually segmented isointense stage brain images. Results showed that our proposed model significantly outperformed prior methods on infant brain tissue segmentation. In addition, our results indicated that integration of multi-modality images led to significant performance improvement. PMID:25562829

Asleep Deep Brain Stimulation Reduces Incidence of Intracranial Air during Electrode Implantation.

PubMed

Ko, Andrew L; Magown, Philippe; Ozpinar, Alp; Hamzaoglu, Vural; Burchiel, Kim J

2018-05-30

Asleep deep brain stimulation (aDBS) implantation replaces microelectrode recording for image-guided implantation, shortening the operative time and reducing cerebrospinal fluid egress. This may decrease pneumocephalus, thus decreasing brain shift during implantation. To compare the incidence and volume of pneumocephalus during awake (wkDBS) and aDBS procedures. A retrospective review of bilateral DBS cases performed at Oregon Health & Science University from 2009 to 2017 was undertaken. Postimplantation imaging was reviewed to determine the presence and volume of intracranial air and measure cortical brain shift. Among 371 patients, pneumocephalus was noted in 66% of wkDBS and 15.6% of aDBS. The average volume of air was significantly higher in wkDBS than aDBS (8.0 vs. 1.8 mL). Volumes of air greater than 7 mL, which have previously been linked to brain shift, occurred significantly more frequently in wkDBS than aDBS (34 vs 5.6%). wkDBS resulted in significantly larger cortical brain shifts (5.8 vs. 1.2 mm). We show that aDBS reduces the incidence of intracranial air, larger air volumes, and cortical brain shift. Large volumes of intracranial air have been correlated to shifting of brain structures during DBS procedures, a variable that could impact accuracy of electrode placement. © 2018 S. Karger AG, Basel.

HORIZONTAL HYBRID SOLAR LIGHT PIPE: AN INTEGRATED SYSTEM OF DAYLIGHT AND ELECTRIC LIGHT

EPA Science Inventory

This project will test the feasibility of an advanced energy efficient perimeter lighting system that integrates daylighting, electric lighting, and lighting controls to reduce electricity consumption. The system is designed to provide adequate illuminance levels in deep-floor...

A computational framework for the detection of subcortical brain dysmaturation in neonatal MRI using 3D Convolutional Neural Networks.

PubMed

Ceschin, Rafael; Zahner, Alexandria; Reynolds, William; Gaesser, Jenna; Zuccoli, Giulio; Lo, Cecilia W; Gopalakrishnan, Vanathi; Panigrahy, Ashok

2018-05-21

Deep neural networks are increasingly being used in both supervised learning for classification tasks and unsupervised learning to derive complex patterns from the input data. However, the successful implementation of deep neural networks using neuroimaging datasets requires adequate sample size for training and well-defined signal intensity based structural differentiation. There is a lack of effective automated diagnostic tools for the reliable detection of brain dysmaturation in the neonatal period, related to small sample size and complex undifferentiated brain structures, despite both translational research and clinical importance. Volumetric information alone is insufficient for diagnosis. In this study, we developed a computational framework for the automated classification of brain dysmaturation from neonatal MRI, by combining a specific deep neural network implementation with neonatal structural brain segmentation as a method for both clinical pattern recognition and data-driven inference into the underlying structural morphology. We implemented three-dimensional convolution neural networks (3D-CNNs) to specifically classify dysplastic cerebelli, a subset of surface-based subcortical brain dysmaturation, in term infants born with congenital heart disease. We obtained a 0.985 ± 0. 0241-classification accuracy of subtle cerebellar dysplasia in CHD using 10-fold cross-validation. Furthermore, the hidden layer activations and class activation maps depicted regional vulnerability of the superior surface of the cerebellum, (composed of mostly the posterior lobe and the midline vermis), in regards to differentiating the dysplastic process from normal tissue. The posterior lobe and the midline vermis provide regional differentiation that is relevant to not only to the clinical diagnosis of cerebellar dysplasia, but also genetic mechanisms and neurodevelopmental outcome correlates. These findings not only contribute to the detection and classification of a subset of neonatal brain dysmaturation, but also provide insight to the pathogenesis of cerebellar dysplasia in CHD. In addition, this is one of the first examples of the application of deep learning to a neuroimaging dataset, in which the hidden layer activation revealed diagnostically and biologically relevant features about the clinical pathogenesis. The code developed for this project is open source, published under the BSD License, and designed to be generalizable to applications both within and beyond neonatal brain imaging. Copyright © 2018 Elsevier Inc. All rights reserved.

Ultrasoft microwire neural electrodes improve chronic tissue integration.

PubMed

Du, Zhanhong Jeff; Kolarcik, Christi L; Kozai, Takashi D Y; Luebben, Silvia D; Sapp, Shawn A; Zheng, Xin Sally; Nabity, James A; Cui, X Tracy

2017-04-15

Chronically implanted neural multi-electrode arrays (MEA) are an essential technology for recording electrical signals from neurons and/or modulating neural activity through stimulation. However, current MEAs, regardless of the type, elicit an inflammatory response that ultimately leads to device failure. Traditionally, rigid materials like tungsten and silicon have been employed to interface with the relatively soft neural tissue. The large stiffness mismatch is thought to exacerbate the inflammatory response. In order to minimize the disparity between the device and the brain, we fabricated novel ultrasoft electrodes consisting of elastomers and conducting polymers with mechanical properties much more similar to those of brain tissue than previous neural implants. In this study, these ultrasoft microelectrodes were inserted and released using a stainless steel shuttle with polyethyleneglycol (PEG) glue. The implanted microwires showed functionality in acute neural stimulation. When implanted for 1 or 8weeks, the novel soft implants demonstrated significantly reduced inflammatory tissue response at week 8 compared to tungsten wires of similar dimension and surface chemistry. Furthermore, a higher degree of cell body distortion was found next to the tungsten implants compared to the polymer implants. Our results support the use of these novel ultrasoft electrodes for long term neural implants. One critical challenge to the translation of neural recording/stimulation electrode technology to clinically viable devices for brain computer interface (BCI) or deep brain stimulation (DBS) applications is the chronic degradation of device performance due to the inflammatory tissue reaction. While many hypothesize that soft and flexible devices elicit reduced inflammatory tissue responses, there has yet to be a rigorous comparison between soft and stiff implants. We have developed an ultra-soft microelectrode with Young's modulus lower than 1MPa, closely mimicking the brain tissue modulus. Here, we present a rigorous histological comparison of this novel ultrasoft electrode and conventional stiff electrode with the same size, shape and surface chemistry, implanted in rat brains for 1-week and 8-weeks. Significant improvement was observed for ultrasoft electrodes, including inflammatory tissue reaction, electrode-tissue integration as well as mechanical disturbance to nearby neurons. A full spectrum of new techniques were developed in this study, from insertion shuttle to in situ sectioning of the microelectrode to automated cell shape analysis, all of which should contribute new methods to the field. Finally, we showed the electrical functionality of the ultrasoft electrode, demonstrating the potential of flexible neural implant devices for future research and clinical use. Copyright © 2017. Published by Elsevier Ltd.

Deep and Structured Robust Information Theoretic Learning for Image Analysis.

PubMed

Deng, Yue; Bao, Feng; Deng, Xuesong; Wang, Ruiping; Kong, Youyong; Dai, Qionghai

2016-07-07

This paper presents a robust information theoretic (RIT) model to reduce the uncertainties, i.e. missing and noisy labels, in general discriminative data representation tasks. The fundamental pursuit of our model is to simultaneously learn a transformation function and a discriminative classifier that maximize the mutual information of data and their labels in the latent space. In this general paradigm, we respectively discuss three types of the RIT implementations with linear subspace embedding, deep transformation and structured sparse learning. In practice, the RIT and deep RIT are exploited to solve the image categorization task whose performances will be verified on various benchmark datasets. The structured sparse RIT is further applied to a medical image analysis task for brain MRI segmentation that allows group-level feature selections on the brain tissues.

Fiber-based tunable repetition rate source for deep tissue two-photon fluorescence microscopy.

PubMed

Charan, Kriti; Li, Bo; Wang, Mengran; Lin, Charles P; Xu, Chris

2018-05-01

Deep tissue multiphoton imaging requires high peak power to enhance signal and low average power to prevent thermal damage. Both goals can be advantageously achieved through laser repetition rate tuning instead of simply adjusting the average power. We show that the ideal repetition rate for deep two-photon imaging in the mouse brain is between 1 and 10 MHz, and we present a fiber-based source with an arbitrarily tunable repetition rate within this range. The performance of the new source is compared to a mode-locked Ti:Sapphire (Ti:S) laser for in vivo imaging of mouse brain vasculature. At 2.5 MHz, the fiber source requires 5.1 times less average power to obtain the same signal as a standard Ti:S laser operating at 80 MHz.

An electrophysiological investigation of memory encoding, depth of processing, and word frequency in humans.

PubMed

Guo, Chunyan; Zhu, Ying; Ding, Jinhong; Fan, Silu; Paller, Ken A

2004-02-12

Memory encoding can be studied by monitoring brain activity correlated with subsequent remembering. To understand brain potentials associated with encoding, we compared multiple factors known to affect encoding. Depth of processing was manipulated by requiring subjects to detect animal names (deep encoding) or boldface (shallow encoding) in a series of Chinese words. Recognition was more accurate with deep than shallow encoding, and for low- compared to high-frequency words. Potentials were generally more positive for subsequently recognized versus forgotten words; for deep compared to shallow processing; and, for remembered words only, for low- than for high-frequency words. Latency and topographic differences between these potentials suggested that several factors influence the effectiveness of encoding and can be distinguished using these methods, even with Chinese logographic symbols.

Mapping the "Depression Switch" During Intraoperative Testing of Subcallosal Cingulate Deep Brain Stimulation.

PubMed

Choi, Ki Sueng; Riva-Posse, Patricio; Gross, Robert E; Mayberg, Helen S

2015-11-01

The clinical utility of monitoring behavioral changes during intraoperative testing of subcallosal cingulate deep brain stimulation is unknown. To characterize the structural connectivity correlates of deep brain stimulation-evoked behavioral effects using probabilistic tractography in depression. Categorization of acute behavioral effects was conducted in 9 adults undergoing deep brain stimulation implantation surgery for chronic treatment-resistant depression in a randomized and blinded testing session at Emory University. Patients were studied from September 1, 2011, through June 30, 2013. Post hoc analyses of the structural tractography patterns mediating distinct categories of evoked behavioral effects were defined, including the best response overall. Data analyses were performed from May 1 through July 1, 2015. Categorization of stimulation-induced transient behavioral effects and delineation of the shared white matter tracts mediating response subtypes. Among the 9 patients, 72 active and 36 sham trials were recorded. The following stereotypical behavior patterns were identified: changes in interoceptive (noted changes in body state in 30 of 72 active and 4 of 36 sham trials) and in exteroceptive (shift in attention from patient to others in 9 of 72 active and 0 sham trials) awareness. The best response was a combination of exteroceptive and interoceptive changes at a single left contact for all 9 patients. Structural connectivity showed that the best response contacts had a pattern of connections to the bilateral ventromedial frontal cortex (via forceps minor and left uncinate fasciculus) and to the cingulate cortex (via left cingulum bundle), whereas behaviorally salient but nonbest contacts had only cingulate involvement. The involvement of the 3 white matter bundles during stimulation of the best contacts suggests a mechanism for the observed transient "depression switch." This analysis of transient behavior changes during intraoperative deep brain stimulation of the subcallosal cingulate and the subsequent identification of unique connectivity patterns may provide a biomarker of a rapid-onset depression switch to guide surgical implantation and to refine and optimize algorithms for the selection of contacts in long-term stimulation for treatment-resistant depression.

Brain changes due to hypoxia during light anaesthesia can be prevented by deepening anaesthesia; a study in rats

PubMed Central

Kalmar, Alain F.; Doorduin, Janine; Struys, Michel M. R. F.; Schoemaker, Regien G.; Absalom, Anthony R.

2018-01-01

In anaesthetic practice the risk of cerebral ischemic/hypoxic damage is thought to be attenuated by deep anaesthesia. The rationale is that deeper anaesthesia reduces cerebral oxygen demand more than light anaesthesia, thereby increasing the tolerance to ischemia or hypoxia. However, evidence to support this is scarce. We thus investigated the influence of light versus deep anaesthesia on the responses of rat brains to a period of hypoxia. In the first experiment we exposed adult male Wistar rats to deep or light propofol anaesthesia and then performed [18F]- Fludeoxyglucose (FDG) Positron Emission Tomography (PET) scans to verify the extent of cerebral metabolic suppression. In subsequent experiments, rats were subjected to light/deep propofol anaesthesia and then exposed to a period of hypoxia or ongoing normoxia (n = 9–11 per group). A further 5 rats, not exposed to anaesthesia or hypoxia, served as controls. Four days later a Novel Object Recognition (NOR) test was performed to assess mood and cognition. After another 4 days, the animals were sacrificed for later immunohistochemical analyses of neurogenesis/neuroplasticity (Doublecortin; DCX), Brain Derived Neurotrophic Factor (BDNF) expression and neuroinflammation (Ionized calcium-binding adaptor protein-1; Iba-1) in hippocampal and piriform cortex slices. The hippocampi of rats subjected to hypoxia during light anaesthesia showed lower DCX positivity, and therefore lower neurogenesis, but higher BDNF levels and microglia hyper-ramification. Exploration was reduced, but no significant effect on NOR was observed. In the piriform cortex, higher DCX positivity was observed, associated with neuroplasticity. All these effects were attenuated by deep anaesthesia. Deepening anaesthesia attenuated the brain changes associated with hypoxia. Hypoxia during light anaesthesia had a prolonged effect on the brain, but no impairment in cognitive function was observed. Although reduced hippocampal neurogenesis may be considered unfavourable, higher BDNF expression, associated with microglia hyper-ramification may suggest activation of repair mechanisms. Increased neuroplasticity observed in the piriform cortex supports this, and might reflect a prolonged state of alertness rather than damage. PMID:29451906

Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making.

PubMed

Coulthard, Elizabeth J; Bogacz, Rafal; Javed, Shazia; Mooney, Lucy K; Murphy, Gillian; Keeley, Sophie; Whone, Alan L

2012-12-01

Even simple behaviour requires us to make decisions based on combining multiple pieces of learned and new information. Making such decisions requires both learning the optimal response to each given stimulus as well as combining probabilistic information from multiple stimuli before selecting a response. Computational theories of decision making predict that learning individual stimulus-response associations and rapid combination of information from multiple stimuli are dependent on different components of basal ganglia circuitry. In particular, learning and retention of memory, required for optimal response choice, are significantly reliant on dopamine, whereas integrating information probabilistically is critically dependent upon functioning of the glutamatergic subthalamic nucleus (computing the 'normalization term' in Bayes' theorem). Here, we test these theories by investigating 22 patients with Parkinson's disease either treated with deep brain stimulation to the subthalamic nucleus and dopaminergic therapy or managed with dopaminergic therapy alone. We use computerized tasks that probe three cognitive functions-information acquisition (learning), memory over a delay and information integration when multiple pieces of sequentially presented information have to be combined. Patients performed the tasks ON or OFF deep brain stimulation and/or ON or OFF dopaminergic therapy. Consistent with the computational theories, we show that stopping dopaminergic therapy impairs memory for probabilistic information over a delay, whereas deep brain stimulation to the region of the subthalamic nucleus disrupts decision making when multiple pieces of acquired information must be combined. Furthermore, we found that when participants needed to update their decision on the basis of the last piece of information presented in the decision-making task, patients with deep brain stimulation of the subthalamic nucleus region did not slow down appropriately to revise their plan, a pattern of behaviour that mirrors the impulsivity described clinically in some patients with subthalamic nucleus deep brain stimulation. Thus, we demonstrate distinct mechanisms for two important facets of human decision making: first, a role for dopamine in memory consolidation, and second, the critical importance of the subthalamic nucleus in successful decision making when multiple pieces of information must be combined.

Decoding of Human Movements Based on Deep Brain Local Field Potentials Using Ensemble Neural Networks

PubMed Central

2017-01-01

Decoding neural activities related to voluntary and involuntary movements is fundamental to understanding human brain motor circuits and neuromotor disorders and can lead to the development of neuromotor prosthetic devices for neurorehabilitation. This study explores using recorded deep brain local field potentials (LFPs) for robust movement decoding of Parkinson's disease (PD) and Dystonia patients. The LFP data from voluntary movement activities such as left and right hand index finger clicking were recorded from patients who underwent surgeries for implantation of deep brain stimulation electrodes. Movement-related LFP signal features were extracted by computing instantaneous power related to motor response in different neural frequency bands. An innovative neural network ensemble classifier has been proposed and developed for accurate prediction of finger movement and its forthcoming laterality. The ensemble classifier contains three base neural network classifiers, namely, feedforward, radial basis, and probabilistic neural networks. The majority voting rule is used to fuse the decisions of the three base classifiers to generate the final decision of the ensemble classifier. The overall decoding performance reaches a level of agreement (kappa value) at about 0.729 ± 0.16 for decoding movement from the resting state and about 0.671 ± 0.14 for decoding left and right visually cued movements. PMID:29201041

Deep brain stimulation for the treatment of uncommon tremor syndromes

PubMed Central

Ramirez-Zamora, Adolfo; Okun, Michael S.

2016-01-01

ABSTRACT Introduction: Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson’s disease however the effectiveness and long-term outcomes of DBS in other uncommon and complex tremor syndromes has not been well established. Traditionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered the main target for medically intractable tremors; however alternative brain regions and improvements in stereotactic techniques and hardware may soon change the horizon for treatment of complex tremors. Areas covered: In this article, we conducted a PubMed search using different combinations between the terms ‘Uncommon tremors’, ‘Dystonic tremor’, ‘Holmes tremor’ ‘Midbrain tremor’, ‘Rubral tremor’, ‘Cerebellar tremor’, ‘outflow tremor’, ‘Multiple Sclerosis tremor’, ‘Post-traumatic tremor’, ‘Neuropathic tremor’, and ‘Deep Brain Stimulation/DBS’. Additionally, we examined and summarized the current state of evolving interventions for treatment of complex tremor syndromes. Expert c ommentary: Recently reported interventions for rare tremors include stimulation of the posterior subthalamic area, globus pallidus internus, ventralis oralis anterior/posterior thalamic subnuclei, and the use of dual lead stimulation in one or more of these targets. Treatment should be individualized and dictated by tremor phenomenology and associated clinical features. PMID:27228280

[Intervening in the neural basis of one's personality: a practice-oriented ethical analysis of neuropharmacology and deep-brain stimulation].

PubMed

Synofzik, M

2007-12-01

Through the rapid progress in neuropharmacology it seems to become possible to effectively improve our cognitive capacities and emotional states by easily applicable means. Moreover, deep-brain stimulation may allow an effective therapeutic option for those neurological and psychiatric diseases which still can not be sufficiently treated by pharmacological measures. So far, however, both the benefit and the harm of these techniques are only insufficiently understood by neuroscience and detailed ethical analyses are still missing. In this article ethical criteria and most recent empirical evidence are systematically brought together for the first time. This analysis shows that it is irrelevant for an ethical evaluation whether a drug or a brain-machine interface is categorized as "enhancement" or "treatment" or whether it changes "human nature". The only decisive criteria are whether the intervention (1.) benefits the patient, (2.) does not harm the patient and (3.) is desired by the patient. However, current empirical data in both fields, neuropharmacology and deep-brain stimulation are still too sparse to adequately evaluate these criteria. Moreover, the focus in both fields has been strongly misled by neglecting the distinction between "benefit" and "efficacy": In past years research and clinical practice have only focused on physiological effects, but not on the actual benefit to the patient.

Monitoring of deep brain temperature in infants using multi-frequency microwave radiometry and thermal modelling.

PubMed

Han, J W; Van Leeuwen, G M; Mizushina, S; Van de Kamer, J B; Maruyama, K; Sugiura, T; Azzopardi, D V; Edwards, A D

2001-07-01

In this study we present a design for a multi-frequency microwave radiometer aimed at prolonged monitoring of deep brain temperature in newborn infants and suitable for use during hypothermic neural rescue therapy. We identify appropriate hardware to measure brightness temperature and evaluate the accuracy of the measurements. We describe a method to estimate the tissue temperature distribution from measured brightness temperatures which uses the results of numerical simulations of the tissue temperature as well as the propagation of the microwaves in a realistic detailed three-dimensional infant head model. The temperature retrieval method is then used to evaluate how the statistical fluctuations in the measured brightness temperatures limit the confidence interval for the estimated temperature: for an 18 degrees C temperature differential between cooled surface and deep brain we found a standard error in the estimated central brain temperature of 0.75 degrees C. Evaluation of the systematic errors arising from inaccuracies in model parameters showed that realistic deviations in tissue parameters have little impact compared to uncertainty in the thickness of the bolus between the receiving antenna and the infant's head or in the skull thickness. This highlights the need to pay particular attention to these latter parameters in future practical implementation of the technique.

Deep brain stimulation of the subthalamic nucleus alters the cortical profile of response inhibition in the beta frequency band: a scalp EEG study in Parkinson's disease

PubMed Central

Swann, Nicole; Poizner, Howard; Houser, Melissa; Gould, Sherrie; Greenhouse, Ian; Cai, Weidong; Strunk, Jon; George, Jobi; Aron, Adam R

2011-01-01

Stopping an initiated response could be implemented by a fronto-basal-ganglia circuit, including the right inferior frontal cortex (rIFC) and the subthalamic nucleus (STN). Intracranial recording studies in humans reveal an increase in beta-band power (~16-20 Hz) within the rIFC and STN when a response is stopped. This suggests that the beta-band could be important for communication in this network. If this is the case, then altering one region should affect the electrophysiological response at the other. We addressed this hypothesis by recording scalp EEG during a stop task while modulating STN activity with deep brain stimulation. We studied 15 human patients with Parkinson's Disease and 15 matched healthy control subjects. Behaviorally, patients OFF stimulation were slower than controls to stop their response. Moreover, stopping speed was improved for ON compared to OFF stimulation. For scalp EEG, there was greater beta power, around the time of stopping, for patients ON compared to OFF stimulation. This effect was stronger over the right compared to left frontal cortex, consistent with the putative right-lateralization of the stopping network. Thus, deep brain stimulation of the STN improved behavioral stopping performance and increased the beta-band response over the right frontal cortex. These results complement other evidence for a structurally-connected, functional, circuit between right frontal cortex and the basal ganglia. The results also suggest that deep brain stimulation of the STN may improve task performance by increasing the fidelity of information transfer within a fronto-basal ganglia circuit. PMID:21490213

Potential subjects' responses to an ethics questionnaire in a phase I study of deep brain stimulation in early Parkinson's disease.

PubMed

Finder, Stuart G; Bliton, Mark J; Gill, Chandler E; Davis, Thomas L; Konrad, Peter E; Charles, P David

2012-01-01

Central to ethically justified clinical trial design is the need for an informed consent process responsive to how potential subjects actually comprehend study participation, especially study goals, risks, and potential benefits. This will be particularly challenging when studying deep brain stimulation and whether it impedes symptom progression in Parkinson's disease, since potential subjects will be Parkinson's patients for whom deep brain stimulation will likely have therapeutic value in the future as their disease progresses. As part of an expanded informed consent process for a pilot Phase I study of deep brain stimulation in early stage Parkinson's disease, an ethics questionnaire composed of 13 open-ended questions was distributed to potential subjects. The questionnaire was designed to guide potential subjects in thinking about their potential participation. While the purpose of the study (safety and tolerability) was extensively presented during the informed consent process, in returned responses 70 percent focused on effectiveness and 91 percent included personal benefit as poten- tial benefit from enrolling. However, 91 percent also indicated helping other Parkinson's patients as motivation when considering whether or not to enroll. This combination of responses highlights two issues to which investigators need to pay close attention in future trial designs: (1) how, and in what ways, informed consent processes reinforce potential subjects' preconceived understandings of benefit, and (2) that potential subjects see themselves as part of a community of Parkinson's sufferers with responsibilities extending beyond self-interest. More importantly, it invites speculation that a different paradigm for informed consent may be needed.

Electrical characterisation of SiGe heterojunction bipolar transistors and Si pseudo-HBTS

NASA Astrophysics Data System (ADS)

De Barros, O.; Le Tron, B.; Woods, R. C.; Giroult-Matlakowski, G.; Vincent, G.; Brémond, G.

1996-08-01

This paper reports an electrical characterisation of the emitter-base junction of Si pseudo-HBTs and SiGe HBTs fabricated in a CMOS compatible single polysilicon self-aligned process. From the reverse characteristics it appears that the definition of the emitter-base junction by plasma etching induces peripheral defects that increase the base current of the transistors. Deep level transient spectroscopy measurements show a deep level in the case of SiGe base, whose spatial origin is not fully determinate up to now.

EQUALIZING THE ELECTRIC FIELD INTENSITY WITHIN CHICK BRAIN IMMERSED IN BUFFER SOLUTION AT DIFFERENT CARRIER FREQUENCIES

EPA Science Inventory

Presented here are the numerical relationships between incident power densities that produce the same average electric field intensity within a chick brain half immersed in buffered saline solution and exposed to a uniform electromagnetic field at carrier frequencies of 50, 147, ...

Patterns of Brain-Electrical Activity during Declarative Memory Performance in 10-Month-Old Infants

ERIC Educational Resources Information Center

Morasch, Katherine C.; Bell, Martha Ann

2009-01-01

This study of infant declarative memory concurrently examined brain-electrical activity and deferred imitation performance in 10-month-old infants. Continuous electroencephalogram (EEG) measures were collected throughout the activity-matched baseline, encoding (modeling) and retrieval (delayed test) phases of a within-subjects deferred imitation…

Performance of deep geothermal energy systems

NASA Astrophysics Data System (ADS)

Manikonda, Nikhil

Geothermal energy is an important source of clean and renewable energy. This project deals with the study of deep geothermal power plants for the generation of electricity. The design involves the extraction of heat from the Earth and its conversion into electricity. This is performed by allowing fluid deep into the Earth where it gets heated due to the surrounding rock. The fluid gets vaporized and returns to the surface in a heat pipe. Finally, the energy of the fluid is converted into electricity using turbine or organic rankine cycle (ORC). The main feature of the system is the employment of side channels to increase the amount of thermal energy extracted. A finite difference computer model is developed to solve the heat transport equation. The numerical model was employed to evaluate the performance of the design. The major goal was to optimize the output power as a function of parameters such as thermal diffusivity of the rock, depth of the main well, number and length of lateral channels. The sustainable lifetime of the system for a target output power of 2 MW has been calculated for deep geothermal systems with drilling depths of 8000 and 10000 meters, and a financial analysis has been performed to evaluate the economic feasibility of the system for a practical range of geothermal parameters. Results show promising an outlook for deep geothermal systems for practical applications.

Effects of brain-computer interface-based functional electrical stimulation on brain activation in stroke patients: a pilot randomized controlled trial.

PubMed

Chung, EunJung; Kim, Jung-Hee; Park, Dae-Sung; Lee, Byoung-Hee

2015-03-01

[Purpose] This study sought to determine the effects of brain-computer interface-based functional electrical stimulation (BCI-FES) on brain activation in patients with stroke. [Subjects] The subjects were randomized to in a BCI-FES group (n=5) and a functional electrical stimulation (FES) group (n=5). [Methods] Patients in the BCI-FES group received ankle dorsiflexion training with FES for 30 minutes per day, 5 times under the brain-computer interface-based program. The FES group received ankle dorsiflexion training with FES for the same amount of time. [Results] The BCI-FES group demonstrated significant differences in the frontopolar regions 1 and 2 attention indexes, and frontopolar 1 activation index. The FES group demonstrated no significant differences. There were significant differences in the frontopolar 1 region activation index between the two groups after the interventions. [Conclusion] The results of this study suggest that BCI-FES training may be more effective in stimulating brain activation than only FES training in patients recovering from stroke.

Implantable optoelectronic probes for in vivo optogenetics.

PubMed

Iseri, Ege; Kuzum, Duygu

2017-06-01

More than a decade has passed since optics and genetics came together and lead to the emerging technologies of optogenetics. The advent of light-sensitive opsins made it possible to optically trigger the neurons into activation or inhibition by using visible light. The importance of spatiotemporally isolating a segment of a neural network and controlling nervous signaling in a precise manner has driven neuroscience researchers and engineers to invest great efforts in designing high precision in vivo implantable devices. These efforts have focused on delivery of sufficient power to deep brain regions, while monitoring neural activity with high resolution and fidelity. In this review, we report the progress made in the field of hybrid optoelectronic neural interfaces that combine optical stimulation with electrophysiological recordings. Different approaches that incorporate optical or electrical components on implantable devices are discussed in detail. Advantages of various different designs as well as practical and fundamental limitations are summarized to illuminate the future of neurotechnology development.

Surgical treatment of Parkinson’s disease: Past, present, and future

PubMed Central

Duker, Andrew P.; Espay, Alberto J.

2013-01-01

Advances in functional neurosurgery have expanded the treatment of Parkinson’s disease (PD), from early lesional procedures to targeted electrical stimulation of specific nodes in the basal ganglia circuitry. Deep brain stimulation (DBS), applied to selected patients with Parkinson’s disease (PD) and difficult-to-manage motor fluctuations, yields substantial reductions in off time and dyskinesia. Outcomes for DBS targeting the two major studied targets in PD, the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi), appear to be broadly similar and the choice is best made based on individual patient factors and surgeon preference. Emerging concepts in DBS include examination of new targets, such as the potential efficacy of pedunculopontine nucleus (PPN) stimulation for treatment of freezing and falls, the utilization of pathologic oscillations in the beta band to construct an adaptive “closed-loop” DBS, and new technologies, including segmented electrodes to steer current toward specific neural populations. PMID:23896506

Implantable optoelectronic probes for in vivo optogenetics

NASA Astrophysics Data System (ADS)

Iseri, Ege; Kuzum, Duygu

2017-06-01

More than a decade has passed since optics and genetics came together and lead to the emerging technologies of optogenetics. The advent of light-sensitive opsins made it possible to optically trigger the neurons into activation or inhibition by using visible light. The importance of spatiotemporally isolating a segment of a neural network and controlling nervous signaling in a precise manner has driven neuroscience researchers and engineers to invest great efforts in designing high precision in vivo implantable devices. These efforts have focused on delivery of sufficient power to deep brain regions, while monitoring neural activity with high resolution and fidelity. In this review, we report the progress made in the field of hybrid optoelectronic neural interfaces that combine optical stimulation with electrophysiological recordings. Different approaches that incorporate optical or electrical components on implantable devices are discussed in detail. Advantages of various different designs as well as practical and fundamental limitations are summarized to illuminate the future of neurotechnology development.

Neuroelectronics and modeling of electrical signals for monitoring and control of Parkinson's disease

NASA Astrophysics Data System (ADS)

Chintakuntla, Ritesh R.; Abraham, Jose K.; Varadan, Vijay K.

2009-03-01

The brain and the human nervous system are perhaps the most researched but least understood components of the human body. This is so because of the complex nature of its working and the high density of functions. The monitoring of neural signals could help one better understand the working of the brain and newer recording and monitoring methods have been developed ever since it was discovered that the brain communicates internally by means of electrical pulses. Neuroelectronics is the field which deals with the interface between electronics or semiconductors to living neurons. This includes monitoring of electrical activity from the brain as well as the development of feedback devices for stimulation of parts of the brain for treatment of disorders. In this paper these electrical signals are modeled through a nano/microelectrode arrays based on the electronic equivalent model using Cadence PSD 15.0. The results were compared with those previously published models such as Kupfmuller and Jenik's model, McGrogan's Neuron Model which are based on the Hodgkin and Huxley model. We have developed and equivalent circuit model using discrete passive components to simulate the electrical activity of the neurons. The simulated circuit can be easily be modified by adding some more ionic channels and the results can be used to predict necessary external stimulus needed for stimulation of neurons affected by the Parkinson's disease (PD). Implementing such a model in PD patients could predict the necessary voltages required for the electrical stimulation of the sub-thalamus region for the control tremor motion.

Representational Distance Learning for Deep Neural Networks

PubMed Central

McClure, Patrick; Kriegeskorte, Nikolaus

2016-01-01

Deep neural networks (DNNs) provide useful models of visual representational transformations. We present a method that enables a DNN (student) to learn from the internal representational spaces of a reference model (teacher), which could be another DNN or, in the future, a biological brain. Representational spaces of the student and the teacher are characterized by representational distance matrices (RDMs). We propose representational distance learning (RDL), a stochastic gradient descent method that drives the RDMs of the student to approximate the RDMs of the teacher. We demonstrate that RDL is competitive with other transfer learning techniques for two publicly available benchmark computer vision datasets (MNIST and CIFAR-100), while allowing for architectural differences between student and teacher. By pulling the student's RDMs toward those of the teacher, RDL significantly improved visual classification performance when compared to baseline networks that did not use transfer learning. In the future, RDL may enable combined supervised training of deep neural networks using task constraints (e.g., images and category labels) and constraints from brain-activity measurements, so as to build models that replicate the internal representational spaces of biological brains. PMID:28082889

Stimulation of the bilateral anterior nuclei of the thalamus in the treatment of refractory epilepsy: two cases of subcortical band heterotopia.

PubMed

Franco, Ana; Pimentel, José; Campos, Alexandre Rainha; Morgado, Carlos; Pinelo, Sara; Ferreira, António Gonçalves; Bentes, Carla

2016-12-01

Subcortical band heterotopia is a neuronal migration disorder that may cause refractory epilepsy. In these patients, resective surgery has yielded inadequate results. Deep brain stimulation of the anterior nuclei of the thalamus has been used for the treatment of refractory epilepsy with good results. We describe the first two patients with subcortical band heterotopia who were submitted to deep brain stimulation of the anterior nuclei of the thalamus, with evaluation of seizure outcome after 12 and 18 months of follow-up. At these times, both showed a >50% decrease in seizure frequency and an increase in seizure freedom. Both patients had a depressive syndrome after surgery that responded fully to anti-depressive medication in one patient and partly in the other. In both, deep brain stimulation of the anterior nuclei of the thalamus was associated with good seizure outcome. This procedure can therefore be considered in the treatment of patients with subcortical band heterotopia and refractory epilepsy. Depression may be a transient adverse event of the surgery or stimulation, however, its aetiology is probably multifactorial.